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89 Cards in this Set
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Marfan Syndrome
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Fibrillin gene on Chromosome 15 & Autosomal Dominant (AD)
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Aortic aneurysm and dissection, aortic root dilation, mitral valve prolapse, long fingers and toes, pectus excavatum or carinatum, scoliosis, pronated feet, lens dislocations, near sightedness.
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Factor V Leiden Deficiency
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a.a substitution in gene for Factor V & AD, incomplete penetrance (10% show phenotype),
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Hypercoagulable state, risk for DVTs, PE. Environmental factors influence the penetrance.
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Huntington Disease
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Gene is Huntingtin in chrom 4p, CAG trinucleotide repeat, coding polyglutamine. Expansion of repeat occurs during paternal meiosis. & AD, age dependant penetrance. Displays anticipation. & Premutation: 27-36 CAG, >40 is Huntington’s Dz.
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Chorea, dementia, personality changes, reduced attention span, poor judgment, occasional psychosis. Degeneration of caudate and putamen. The greater the # of repeats, the earlier the onset and the greater the severity.
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Waardenburg’s syndrome
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Mutated pax3 gene on chromosome 2 & AD, variable expressivity
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Leads to defect in neural crest cell migration during embryogenesis. Deafness, pigmentary changes, characteristic facies,
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Cystic Fibrosis
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Mutation in CFTR – ∆F508 (chloride channels) & Autosomal recessive (AR)
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Increased sweat chloride content, lung disease, pancreatic insufficiency, male infertility,
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Hemachromatosis
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Mutation in HFE gene involved in iron transport by binding transferrin receptor & AR, incomplete penetrance and variable expressivity
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Cirrhosis and increased risk for HCC, arthritis, skin bronzing, cardiomyopathy, diabetes mellitus, testicular atrophy. Not all will have the same pattern of phenotype, and it has incomplete penetrance.
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Hemophilia A
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Factor VIII mutation, part of the clotting cascade & Sex-linked recessive
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Inability to form clots, common to bleed into the joint space or the gut. Hemophilia B – Factor IX.
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MELAS
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MERF and MELAS are point mutations. Kearns-Sayre is a large scale mitochondrial deletion & Mitochondrial inheritance, usually all children of an affected mother are affected. MERF, MELAS, Kearns-Sayre syndrome all show maternal mitochondrial inheritance.
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MERF is myoclonus epilepsy with ragged red fibers. MELAS is mitochondrial myopathy encephalopathy, lactic acidosis, stroke like episodes. KS patients show weakness in extraocular muscles. NARP = neuropathy ataxia with retinitis pigmentosa. LHON = leber hereditary optic neuropathy
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Prader-Willi Syndrome
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Microdeletion in chromosome 15. This is imprinting, where gene expression occurs from only one parent’s allele. & Imprinting OR maternal uniparental disomy. Diagnose w/FISH.
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Phenotype depends on which parent you inherit the mutation from – in this case the father. Failure to thrive, hypotonia, mild to moderate MR, childhood obesity,
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Angelman syndrome
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Microdeletion in chromosome 15 (identical to Prader-Willi deletion). Diagnose w/FISH. & Imprinting, or single point mutation in SNRPN gene.
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Phenotype depends on which parent you inherit the mutation from – the mother in Angelman’s. Small body, severe MR, marionette-like scissoring gate aka “happy puppet”.
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Williams Syndrome
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Microdeletion in 7q1
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Mild MR, characteristic facies, aortic stenosis, unique personality of overfriendliness & possible exceptional musical talents.
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McCune-Albright syndrome
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Activating mutation in alpha subunit of the G protein that regulates intracellular signaling. & Autosomal dominant Non-Viable
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The mutation is not inherited, because if it was, the fetus would be non-viable. The mutation arises in the embryo and is confined to a patch of tissue. See multiple endocrine tumors that may progress to malignancy.
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Rett syndrome
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Mutation on X chromosome. & Sex-linked dominant. Not inherited usually d/t low repro fitness
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Severe MR with progressive encephalopathy seen only in girls b/c males with mutation die in utero.
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Leri-Weill dyschondrosteosis
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Mutation in the SHOX homeobox transcription factor & Pseudoautosomal inheritance
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A form of dwarfism. Pseudoautosomal regions of the Y chromosome are found at the tips of both the long and short arms.
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Achondroplasia
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Single BP mutation leading to a.a. substitution in FGFR3 (fibroblast growth factor receptor) & AD, usually result of a new mutation
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Form of dwarfism, Associated with advanced paternal age.
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Tay-Sachs disease
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Loss of fx in neuraminidase gene. Neuraminidase breaks down sphingolipids, and without it, the neurons become packed with cellular debris (lipids) & AR, associated with founder effects
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Early childhood onset neurodegenerative disease. Common in Ashkenazi Jews. Leads to death well before puberty
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G6PD
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Loss of glucose-6-P dehydrogenase. & Sex linked recessive
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Hemolytic anemia after exposure to oxidants (including fava beans, quinine-based anti-malarials, and sulfa antibiotics). Heterozygote advantage against malaria.
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Down Syndrome
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Trisomy 21 & Maternal nondisjunction (associated with advanced maternal age -AMA)
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Hypotonia, flat nasal bridge, upslanting palpebral fissures, epicanthal folds, brushfield spots of iris, flat midface, small dysplastic ears, protruding tongue, brachycephaly, excess nuchal skin, short broad hands, single palmar crease, congenital heart disease (Endocardial cushion defects), duodenal atresia. Later in life, increased risk of leukemia, hypothyroidism, and early onset Alzheimers
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Trisomy 18
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Trisomy 18 & Maternal nondisjunction, AMA
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Prenatal growth retardation, small ears, small mouth, small jaw (micrognathia), congenital heart disease, severe MR. Clenched hand, hypotonia, rocker bottom feet, prominent occiput. 50% mortality by one month of age.
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Trisomy 13
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Trisomy 13 & Maternal nondisjunction and AMA
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Midline defects such as holoprosencephaly, cleft lip/palate, microphthalmia, congenital heart disease, renal abnormalities, postaxial polydactyly, cutis aplasia, severe MR. Survival similar to trisomy 18.
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Turner Syndrome
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45X (missing 1 X), females only affected & Paternal non-disjunction (50%), 30-40% are mosaic 45X/46XX
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Short, lymphedema (puffy hands & feet), webbed neck, broad chest, widely spaced nipples, cubitus valgus, congenital heart disease (coarcted aorta), kidney probs, gonadal dysgenesis, amenorrhea, infertility. Normal intelligence, difficulties w/spatial perception.
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Klinefelter Syndrome
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47, XXY (extra X chromosome in males) & AMA, extra X is maternal in origin
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Tall, eunuchoid habitus, gynecomastia, testicular atrophy, infertility. Lower IQ compared to sibs. Can be reversed (except for infertility) w/testosterone tx.
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47 XXX
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Same: 47, XXY (extra X chromosome in males) & Maternal nondysjunction
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Tall for their families, slight reduction in IQ, fertility is normal.
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47, XYY
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Same: 47, XXY (extra X chromosome in males)
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Normal, taller than avg, maybe slightly lower IQ, NOT more inclined to violence, some ADHD?
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Cri-du-Chat
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Deletion of 5p (5p-). Terminal deletion syndrome that can be seen on Giemsa staining. & Most are new mutations, some are result of bal. rearrangements.
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Cat-like cry, microcephaly, growth retardation, unique facies, severe MR.
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Velocardiofacial Syndrome (VCFS)
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Deletion of chromosome 22 at q11.2. Microdeletion syndrome. & AD, diagnose w/FISH, variability of phenotype
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Submucous cleft palate (velo), conotruncal heart disease (cardio), unique facies (facial), learning probs, mental illness.
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DiGeorge Syndrome
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Deletion of 22q11.2, microdeletion syndrome. & AD, diagnose w/FISH.
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Conotruncal heart disease, absent or hypoplastic thymusimmune deficiency, sm/absent parathyroid glands hypocalcemia.
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Fragile X Syndrome
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Mutation in FMR1 at Fragile X site, mutation is CGG expansion & *Sperm of affected males has only the permutation, so children won’t be affected, daughters will be carriers. & Sex linked recessive, repeats expand only during female meiosis. 50% of females are penetrant. Displays anticipation. & 8-50 CGG repeatsnormal, 50-200 is premutation carrier, 200-1000 is Fragile X. If have less than 90 repeats, 80% chance it will expand during meiosis. If more than 90, 100% chance of expansion.
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Dysmorphic features (long face, prominent ears, jaw, forehead), severe MR, macrorchidism, hyperextensible joints. Premutation carrier females can have premature ovarian failure.
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Myotonic Dystrophy
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CTG repeat expansion in chrom. 19q protein kinase gene (DMPK) that is expressed in muscle. & Genetically heterogenous: can be caused by CCTG expansion in 3q (CNBP). & AD, expansion of repeats in maternal meiosis, displays anticipation.
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Myotonia (hard to release after making fist), myopathic weakness, ptosis, open mouth, cardiac arrhythmia, cardiomyopathy, testicular atrophy, cataracts, predisposition to diabetes. Congenital form has onset at birth w/hypotonia, respiratory & feeding probs, MR should child survive.
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Alzheimer’s Disease
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APP (amyloid precursor protein) gene on chrom 21, or presinilin 1 (chrom 14), presinilin 2 (chrom 1), apolipoprotein e4 on chrom 19. & Complex genetics, single gene disorder, or non-genetic (such as head injury)
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Dementia. Neuritic senile plaque & neurofibrillary tangles on autopsy.
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Pelizaeus-Merzbacher Disease (PMD)
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Mutations in MLP (myelin proteolipid) protein PLP1 & X linked recessive, displays allelic heterogeneity
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Leukodystrophy usually of childhood onset, spasticity, autonomic dysfunction, cerebellar disturbance.
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CADASIL (cerebral AD arteriopathy w/subcortical infarcts & leukoencephalopathy)
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Mutation in NOTCH3, a transmembrane receptor whose proteolytic product translocates to nucleus to activate genes & AD
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It’s all in the name…apparently…
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Wilson’s Disease
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Mutation in copper transporter gene in chrom 13 lead to basal gangliar degeneration. & AR
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Hepatic insufficiency, possible chorea & behavior changes, Kayser-Fleischer rings in iris (copper deposits).
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Dentatorubral-Pallidolysian Atrophy (DRPLA)
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CAG triplet expansionbasal gangliar degeneration. & AD
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?
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Parkinson Disease
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Mutation in alpha-synuclein gene or Parkin (in juvenile) & AR or AD
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Bradykinesis, rigidity, tremor, dystonia, neuronal loss in substantia nigra. Neurofibrillary plaques.
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Spinal Cerebellar Ataxia
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SCA6 (CAG triplet repeat expansion in a calcium channel gene) & AD
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Adult onset ataxia (poorly coordinated movement), hyperreflexia, upper motor neuron signs, progressive. Cerebellar atrophy!
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Friedrich Ataxia
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Mutation in frataxin gene w/GAA repeat expansion. & AR
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Hypoactive reflexes, cardiomyopathy, childhood onset.
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Amyotrophic Lateral Sclerosis (ALS)
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mutation in SOD gene on chrom 21 (a copper/zinc oxide dismutase) & Variable, sporadic or AD
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Motor fxn loss (upper and lower motor neuron)
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Kennedy Spinobulbar Muscular Atrophy (SBMA)
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Mutation in CAG triplet repeat in androgen receptor gene on X chromosome & X linked recessive
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Lower motor neuron involvement, muscle weakness & atrophy, androgen insensitivity (loss of male secondary sex characteristics).
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Familial Spastic Paraparesis
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Spastin, Spartin, and atlastin mutations (NOT triplet repeats!). Genetically heterogenous disorders. & AR, AD, X linked
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Lower extremity motor weakness & spasticity due to upper motor neuron disease.
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Charcot-Marie-Tooth (CMT)
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Mutation in PMP-22 on chrom 17 (most common), duplication in PMP22 & AD
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Distal arm and leg muscle atrophy and weakness. Two different types (same phenotype, different mutations). Nerves are often enlarged, slowing nerve conduction velocity.
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HNPP (Hereditary Neuropathy & Pressure Palsies)
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Deletion in PMP-22 on chrom 17 & AD
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Increased pressure palsies and transient motor weakness upon compression of nerves.
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Duchenne Muscular Dystrophy
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Mutation in dystrophin on X chromosome & Sex-linked recessive
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Weakness of proximal limb girdles of upper and lower extremity, wheelchair bound by puberty, don’t usually survive to adulthood, Gower’s sign, pseudohypertrophic calf muscles, some degree of MR, cardiomyopathy possible. Mostly affects males, but females can be mildly affected.
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Becker Muscular Dystrophy
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Mutation in dystrophin on X chromosome & Sex-linked recessive
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Milder than Duchenne’s. Later onset, less severe symptoms.
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Sex linked severe combined immunodeficiency
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Mutation in the gene for IL-2 receptor gamma chain & Sex linked recessive,
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IL2RG delivers growth, survival, and differentiation signals to early lymphoid progenitors. Absence of T lymphocytes and low antibodies. Opportunistic infec. Gene therapy success story.
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Coronary Heart Disease
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Multiple. LDL receptor, environmental factors, cholesterol genes etc…. & Complex inheritance pattern
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Women have a higher threshold for disease than men. If mom has it, then you are at greater risk to have it (compared to if your father had it). Recurrence risk for complex diseases is proportional to population risk. Recurrence risk lower for more distant relative.
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Bipolar Affective Disorder
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Because of twin studies, we have found that Bipolar disorder is likely to be heritable.
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Same with body fat percentage.
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Multiple Endocrine Neoplasia 2
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RET mutation – a proto-oncogene & AD
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Inherited cancer predisposition syndrome. Medullary thyroid carcinoma, parathyroid adenoma, pheochromocytoma.
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Familial Renal Cell Carcinoma
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MET proto-oncogene & AD
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Renal cell carcinoma. *RET & MET are the only 2 examples of inherited mutations in proto-oncogenes!
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Retinoblastoma
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RB gene (regulates transit through cell cycle) & AD
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Gene is tumor suppressor. Get the disease once you get a mutation in your good copy of the gene. Tumor of the retinal epithelium, high risk for secondary tumors (osteosarcoma, fibrosarcoma, melanoma).
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RB microdeletion syndrome
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Deletion in the RB gene (on chromosome 13, 13q14.1-q14.2). Tumor suppressor. & AD, sporadic
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Congenital abnormalities and MR (plus above disease),
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Li-Fraumeni
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p53 mutations in germline cells (guardian of the genome). Tumor suppressor. & AD
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p53 is a tumor suppressor, whose expression is induced by DNA damage and it regulated apoptosis. Multiple malignancies, breast cancer, sarcoma, osteosarcoma, brain tumors, leukemia, adrenocortico carcinoma
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Neurofibromatosis 1 (Tumor suppressor)
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Neurofibromin gene (a GTPase activating protein), loss of fx mutation resulting in GTP build-up in cells. & AD
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Syndrome of benign tumors known as neurofibromas, can occasionally become malignant. Schwannoma, glioma, pheochromocytoma, and leukemia. Café-au-lait spots, fleshy neurofibromas, hamartomatous lesions of iris, axillary freckling,
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Von Hippel-Lindau Syndrome
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VHL gene (involved in signaling response to tissue hypoxia). Tumor suppressor. & AD
Either LOH or a CpG rich region in the VHL promoter becomes "hypermethylated" at the cytosines, switching off transcription of the gene and thereby leading to loss of transcription without mutation |
Benign vascular tumors of cerebellum and retina (hemangioblastoma), pheochromocytoma, and RCC.
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Familial adenomatous polyposis
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APC mutations, a tumor suppressor gene involved in cell cycle progression. & AD
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Polyps by early adulthood. Inevitable colon adenocarcinoma (tx prophylactically with colon removal).
occasionally extracolonic manifestations incl. fundoscope lesion CHRPE (congenital hypertrophy of the retinal pigment epithelium) and benign subcutaneous and bone cysts (Gardner's syndrome) |
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Familial Breast Cancer/Ovarian Cancer
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BRCA1 and BRCA2. & BRCA2 more common in male breast cancer. BRCA1 is more common in ovarian. Tumor suppressor. & AD, sporadic
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5% of all breast cancer is familial. Familial breast cancer tends to show up earlier, have bilateral tumors, and have a prevalence of ovarian cancer and male breast cancer. Beware of phenocopies (someone with the disease without the inherited genetic mutation). If women have a mutation in either BRCA, lifetime risk of breast cancer is 50-80%, and 25% for ovarian cancer. Men inheriting the mutation have a lifetime risk of 6%.
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Cowden’s syndrome
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Mutation in PTEN gene (a p53 inducible phosphatase). Tumor suppressor. & AD
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Breast cancer, characteristic subtle skin lesions, thyroid disease/cancer, benign colon polyps.
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Ataxia-telangiectasia
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Mutation in ATM gene (recognizes broken chromosomes and allows time for DNA repair) & AD
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Increased risk for hematopoietic malignancies, ataxia, telangiectasias on the skin, (Heterozygous carriers at risk for breast cancer)
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Bloom’s syndrome
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Mutations in DNA helicase (results in high freq. sister chromatid exchanges) RECQL3 & AD
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Elevated risk for hematopoietic malignancy. (Heterozygous carriers at risk for colon cancer)
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Fanconi syndrome
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Genetically heterogenous, but all function in DNA repair & AD
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Variety of birth defects – including horse shoe kidney. Increased risk for developing acute myelogenous leukemia (AML). Cells sensitive to DNA alkylating agents during mitosis. Aplastic anemia develops.
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Xeroderma pigmentosum
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Genetically heterogenous, cellular defect in excision repair of thymine dimers & AD
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Risk for developing skin cancer upon exposure to UV light.
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HNPCC – hereditary non-polyposis colorectal cancer
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MSH2 is most common mutation. MLH1 less common. All genes involved in DNA mismatch repair. & AD
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Mutation results in genetic material that has lots of mismatched DNA. Colon, GI, endometrium, ovarian cancers. HNPCC is 5-10% of all colon cancer. Microsatellite instability.
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Phenylketonuria (PKU)
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Deficiency of phenylalanine hydroxylase (PAH), which converts phenylalaninetyrosine & AR, allelic heterogeneity
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Phenylalaninemia, normal at birth but w/o treatment develop microcephaly, seizures, progressive psychomotor retardation, autistic-like features over 1st yr of life. Eczema, blond hair, blue eyes, pale skin, musty odor. 1-2% of these individuals will also have a defect in synthesis/recycling of tetrahydrobiopterin (a cofactor for PAH). Tyrosine levels are reduced.
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Maple Syrup Urine Disease (MSUD)
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Deficiency of the decarboxylase (encoded by genes on 3 different autosomal chrom) that acts upon branched-chain aa’s (leucine, isoleucine, valine, essential in the diet b/c can’t be metabolized!). Cofactor= thiamine. & AR
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Elevations in levels of the 3 branched chain aa’s, odorous (like maple syrup) urine, skin, scap. “Classic MSUD”- infants normal at birth, within days develop lethargy, abnormal tone, seizures, progressing to cerebral edema and coma. “Mild MSUD” is less intense & enzyme has residual activity. “Thiamine responsive MSUD” has milder presentation than “classis” and patient’s respond to high doses of thiamine, increases the enzyme’s activity.
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Methylmalonic Aciduria (MMA)
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Deficiency of methylmalonyl-CoA mutase (converts methylmalonyl-CoA succinyl-CoA, which can enter the Krebs cycle), involved in catabolism of isoleucine, valine, methionine, threonine. & AR
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Methylmalonic acid accumulates in blood & urine, normal baby at birth, w/onset of lethargy, ketoacidosis (NOT seen in MSUD), progressing to cerebral edema & coma. * Can have defects in the enzyme, it’s cofactor (B12), or enzyme transporter.
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Biotinidase Deficiency (biotin is water-soluble B complex vitamin, normally derived from the diet, needed for activity of many enzymes).
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Deficiency of either holocarboxylase synthetase (attaches biotin to carboxylase enzymes) or biotinidase (recycles biotin by cleaving it off aa’s, more common). & AR
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Both disorders involve seizures, hypotonia, lethargy, developmental delay, skin rash, alopecia, metabolic acidosis, organic aciduria (low urine pH).
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Smith-Lemli-Opitz Syndrome (SLO)
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Deficiency of 3 beta-hydroxysterol-delta 7 reductase, involved in synthesis of cholesterol. [Diagnosis: measure cholesterol levels (low) & cholesterol metabolites (eg, 70-hydrchol., high) & AR
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Characteristic facies, microcephaly, 2,3 toe syndactyly, cardiac defects, developmental delay, short stature, hypogenitalism (males). Unique among metabolic dz in that it resembles an autosomal aneuploidy (multiple congenital abnormalities, growth/developmental delays)!
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MPS type 1H (Hurler Syndrome) (MPS= mucopolysaccharidosis)
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Deficiency of alpha-iduronidase, leading to intralysosomal accumulation of heparin sulfate & dermatan sulfate. & AR . & Therapy by IV enzyme replacement. Tag enzymes w/mannose-6-phosphate to get it where it needs to go. Problem: doesn’t cross BBB.
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Lysosomal storage disease caused by disorders of lysosomal degradation of MPS (aka glycosaminoglycans, mucopolysaccharides), critical components of CT. Normal at birth, soon develop coarse features caused by thickened tissues, hepatosplenomegaly (protuberant tummy), corneal clouding, upper airway problems, claw hand deformity. Later, gross upper airway obstruction, macrocephaly w/ or w/o hydrocephalus, delay followed by regression of mental development. Cardiac & neurodegenerative dz by mid-childhood, death by age 10.
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Galactosemia
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Deficiency of GALT (galactose 1-phosphate uridyl-transferase), galactokinase, or uridine diphosphate galactose 4-epimerase, which convert galactose to glucose. & AR
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Elevated blood & tissue levels of galactose (toxic!), cataracts, developmental delay, liver disease, ovarian failure in females. *Lactose (diet, milk)glucose + galactose. Ecoli sepsis predisposition.
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Congenital Adrenal Hyperplasia (CAH)
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Enzymatic defects in synthesis of cortisol, a steroid hormone made in the adrenal cortex in response to stress. 90% cases caused by 21-hydroxylase deficiency. & AR
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Accumulation of steroid precursors prior to the block (progesterone & 17-hydroxyprogesterone) are shunted through androgen biosynthetic pathway ambiguous genitalia in females, postnatal virilization in both sexes. Plus or minus “salt wasting”.
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Congenital Hypothyroidism
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Heterogenous, developmental defects of thyroid, TSH insensitivity, T4/3 insensitivity, defects in synthesis of T4, etc.
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Edema, sluggishness, hypothermia, followed later by growth & developmental retardation.
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Sickle Cell Disease
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Sickle cell “S” allele results from glutamatevaline substitution in beta-chain of Hemoglobin. & AR, heterozygous carriers are unaffected, carrier frequency is African American population is 8% (2pq), occurs (q2) in ~1/625 births.
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During hypoxemia or high Hgb concentration the abnormal Hgb S aggregates, causing RBCs to assume sickle shapevasocclusive crisesinfarction of spleen, brain, BM, kidney, lung, aseptic necrosis of bone, gallstones, priapism, ankle ulcers.
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Beckwith-Wiedemann Syndrome
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defects in normal expression of imprinted genes on chromosome 11p15
2x expression of IGF2 because of too much dad |
childhood overgrowth condition with a cancer predisposition
large for gestational age, may have neonatal hypoglycemia, an omphalocele or umbilical hernia, a large tongue and ear creases and pits; asymmetric growth or hemihyperplasia, Wilms tumor (kidney cancer) or hepatoblastoma |
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Russell-Silver Syndrome
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loss of methylation on 11p15 at DMR1 near the IGF2
or maternal uniparental disomy |
prenatal and postnatal growth retardation, proportionate short stature, frequent body asymmetry, normal head circumference with an upside down triangular-shaped face.
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Kearns-Sayre Syndrome
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large scale deletion in mitochondria DNA
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muscle weakness, heart failure, and cerebellar damage
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Pearson Syndrome
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large scale deletion in mitochondria DNA
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infantile pancreatic insufficiency, pancytopenia, lactic acidosis
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Chronic progressive external ophthalmoplegia
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large scale deletion in mitochondria DNA
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CPEO, weakness of the orbit coordinating eye movement
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Multiple Endocrine Neoplasia
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inherited mutation in RET proto-oncogene
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high frequency of medullary thyroid carcinoma, parathyroid adenoma, and pheochromcytoma of the adrenal and related tissue
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Familial Renal Cell Carcinoma
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AD inheritance of the MET proto-oncogene
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Kidney Cancer
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WAGR Syndrome
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microdeletion of WT1 on crhomosome 11p13
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Wilim's tumor, aniridia, genitourinary abnormalities, mental and growth retardation
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Smith-Magenis
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deletion of 17p11.2
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Mental retardation, dysmorphic features, unique behavioral features
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Fetal Alcohol Syndrome
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chronic alcohol exposure during pregnancy
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craniofacial differences, small head, short eyelid width, smooth philtrum between upper lip and nose and thin upper lip; behavioral problems and developmental disability, growth deficiency, and occasional CNS, heart and renal anomalies
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Huntington disease-like 1 (HDL1)
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AD, specific mutation in the prion protein (PrP) gene, PRNP, on chromosome 20p
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early-onset, slowly progressive prion disease
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Huntington disease-like 2 (HDL2)
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AD
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presents with a relentless progressive triad of motor, cognitive, and psychiatric abnormalities progressing to death over ten to 20 years - highest prevalence among African decent
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Autosomal Dominant Hereditary Ataxias
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most common mechanism of mutation is a triplet repeat expansion of CAD encoding polyglutamine tract in the protein
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heterogenous diseases known as spinocerebellar ataxia (SCA)
adult onset ataxia hyperreflexia upper motor neuron signs progressive |
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Atuosomal Recessive Ataxias & Friedreich ataxia
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novel triplet repeat GAA expansion in the first intron of the FXN gene, encoding frataxin, that appears to be a mitochondrial iron transporter
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severe progressive disease with childhood onset; cardiomyopathy, hypoactive reflexes
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Homocystinuria
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impaired metabolism of homocysteine by decreased activity of cystathionine betasynthase (CBS) & AR
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Marfanoid habitus (tall, slender, long extermities, high arched palate, scoliosis, pectus excavatum sternal defect), and bilateral optic lens dislocation with myopia, light-colored dry hair, moderate mental retardation, and significantly increased risk for thromboemboic disease; screen by elevated levels of homocysteine in blood or deficient CBS activity; Tx with oral pyridoxine 50% responsive
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abacavir hypersensitivity
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Only individuals with the HLA‐B*5701 allele are susceptible to this hypersensitivity reaction.
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fever, malaise, dizziness, headache, nausea, vomiting,
diarrhea, dyspnea and cough that appears one‐to‐three weeks after starting treatment |
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deficiency of thiopurine
methyltransferase (TPMT) |
TPMT inactivates 6‐mercaptopurine and azathioprine, drugs used in
leukemia chemotherapy, immunosuppression to prevent rejection of organ transplants or treatment of autoimmune diseases. |
exposure to thiopurine drugs can
lead to life‐threatening bone marrow toxicity |
