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200 Cards in this Set

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which disorder is related to mutations of a SINGLE gene of LARGE effect? (heritable)
Mendelian disorders
which disorder occurs where phenotypic expression of disease is related to the combined effect of enviornmental influences and mutliple gene mutations of SMALL effect (polygenic inheritance)?
disorders with multifactorial inheritance
which disorder is known as a chromosomal disorder? they are diseases arising from chromosomal abberations that are identifiable on a karyotype.
cytogenic disorders
which disroder has triplet repeat mutations, mutations in mitochondral genes and genomic imprinting?
single-gene disorders with atypical patterns of inheritance.
i am derived from one's parents and i am transmitted in the gametes through the generations.
hereditary
i am a type of abnormality that is present at birth. i may or may not be genetic. what term describes me?
congenital
i am passed on through the generations of a family. i may appear sporadically. what term defines me?
Familial
there are 3 traditional classifications of diseases. what are they?
1. genetically determined
2. environmentally determined
3. both genetic and environmental factors determined
what is a functional unit which occurs at a unique locus on a chromosome and determines a specific hereditary trait?
a gene
what is the actual genetic code present at a gene locus?
genotype
what is the observable physical characteristc seen expressed by the genetic code?
phenotype
T/F: each person has 2 genes coding for 1 physical trait.
T
T/F: each gene is located at the same locus in each of the paired consitutent chromosomes and is referred to as an allele.
T
what is a mutation, in a few words
any permanent change in DNA
changes in genes = genotype.
changes in proteins they code for = phenotype.
T/F?
T
T/F: mutations in somatic cells can be transmitted to the offspring.
F. only sex cells.
what is a disease caused by mutation of a gene located on one of the 44 autosomes (non-sex chormosomes)?
autosomal disorder
disease is caused by mutation of a gene located on the X-chromosome.
x-linked disorder.
disease that is expressed in the phenotype if the mutation is present in the genotype, ex both heterozygotes and homozygotes express the disease
dominant disorder
disease that is expressed in the phenotype only if BOTH gene loci of the chormosome pair have hte pathologic mutation (homozygotes) or heterozygotes for the gene mutation are clinally normal but are disease carriers
recessive disorder
Codominance is when both allels of the gene pair are fully expressed in the heterozygote. T/F?
T
what is pleiotrophy?
a single-gene mutation that may cause many phenotpyic effects
a single gene mutation at any of several different gene pairs may cause the SAME phenotypic disease
genetic heterogeneity. ex: CF
what are the 3 autosomal dominant medelian disorders?
Familial Hyperchoesterolemia
Marfan Syndrome
Neurofibromatosis Type 1
what disease has an incidence of 1:500?
Familial hypercholesterolemia
what is the most common mendelian disorder overall?
familial hypercholeserolemia
a mutation involving the gene specifing for low-density lipoprotein(LDL) is what disease?
familial hypercholesterolemia
what are xanthomas and which disease can they be found in?
xanthoma = cholesterol deposits formed along tendon sheaths seen in familial hypercholesterolemia
in FH, elevated serum cholesterol can be seen. Heterozyotes have a 2-3 fold increase. what do homozygotes have?
a >5 fold increase
at least 16 different gene mutations can cause the condition of FH. this can be related to what term?
genetic heterogeny
what incidence is 1:20,000
Marfan Syndrome
what has a mutation in the fibrillin 1(FBN1) gene?
Marfan syndrome
how are ehlers danlos and marfan syndrome different?
Ehler Danlos = weak CT. Marfan = major collagen fibers and elastic fibers are structurally NORMAL, however there is fragmentation of ELASTIC TISSUE.
hyper extendable joints and joint dislocations and elongated slender fingers can be seen in what disease?
marfan syndrome
what is the biggest problem in marfan's syndrome?
cardiovascular = floppy heart valves, regurgitation, possible CHF
bilateral dislocation of the lens, arachnoid fingers and aortic dilation can be seen in what?
marfan syndrome
what has an incidence of 1:3,000 that is an autosomal dominant disorder of menelian descent?
Neurofibromatosis type 1
which type of neurofibromatosis (type 1 or 2) accounts for > 90% of all neurofibromatosis?
type 1
mutation in what gene is found in NF type 1?
NF1 gene
the NF1 gene is a tumor supressor gene. T/F
T
what are clinical features of NFtype1?
-multiple neurofibromas (esp the plexiform type)
-cafe-au-lait spots
-pigmented hamartomas of the iris = LISCH NODULES
-malignant transformation (3% of all pts)
Lisch nodules are what?
pigmented hamartomas
cafe-au-lait spots can be seen in what?
Neurofibromatosis type 1
Cystic Fibrosis is an autosomal recessive disorder caused by mutatiosn of what gene?
CFTR
CFTR gene codes for a membrane associated protein that serves as a ________ channel
chloride
70% of patients have disease attributable to a single mutation. there are over 300 recognized mutations for the CFTR gene. this can be described by what term?
genetic heterogeneity
in CF the epi cells are impermeable to Cl ions = causing mucus secretions to be very viscid and sweat gland secretions to be abnormally _______.
salty
what chromosome can CF be found on?
7q31-31
what test is used for CF?
sweat chloride test
what test is used for CF carriers and for prenatal diagnosis?
DNA probes
what is the age of onset of CF?
infancy/early childhood
recurrent and chronic pulmonary infections are seen 100% of hte time in CF. what organisms are responsible?
pseudomonas aeruginosa
staph aureus
in what disease do you see pancreatic insufficiency and malabsorption?
CF
what would hte stools look like in a CF patient?
fatty floaties
what are the main complications of CF?
-mucus plug & bronchietasis
-chronic bronchitis
-Lung abscesses
in CF, the prognosis median life expentancy is now how many years?
30 yrs
80-90% of CF patients die of what?
respiratory infections
what disease has an incidence of 1:12,000 with scandinavians more at risk than asians/blacks?
PKU
a mutation in enzyme proteins that is an autosomal recessive mendelian disorder is?
PKU
in PKU what is the enzyme severely lacking?
phenylalanine hydroxylase
what does phenylalanine hydroxylase do?
converts phenylalanine to tyrosine
what is the age of onset of PKU?
within weeks of birth.
if PKU is not treated in the 1st six months of life what will you see?
severe mental retardation
what causes the severe mental retardation in PKU?
excess serum phenylalnine enters the brain causing impaired brain development. IQ = 50-60
a decrease in tyrosine will cause the skin/hair of the baby to be lighter or darker? and why?
lighter. bc decrease tyrosine = decrease melanin syntheis.
what is the treatment of PKU?
dietary restriction of phenylalanine in early life
-BH4 = tetrahydrobiopterin
-mom should not eat phenylalanine either
in PKU, what does BH4 do?
this enzyme coworker helps break down the phenylaaline molecule
what disease has an incidence of 1:57,000 and is an autosomal recessive disorder of mendelian desecent?
Galactosemia
autosomal recessive disorder of galactose metabolism can be seen in ?
galactosemia
lactose from milk is metabolized to glucose and _______.
galactose
in the most common form of galactosemia, there is a TOTAL lack of what enzyme?
Galactose-1-phosphate uridyl transferase which prevents further metabolism of galactose-1-phosphate
in the rare form of galacosemia, there is deficiency of what enzyme?
galactokinase
failure to thrive, with vomiting and diarrhea, cataracts, CNS changes, hepatomegaly and jaundcie are clinical features of what disease
galacatosemia
what is cataracts?
galactose deposits in the lens of eye, changing the osmotic pressure
why is there hepatomegaly and jaundice in galactosemia?
large liver due to storing galactose, hepatocytes can't do normal activity
mental retardation can be seen in galactosemia and PKU. which is more severe and sooner seen?
PKU
what is the treatment of galactosemia?
galactose free diet for first TWO years of life. a MILK FREE DIET!
what are the lysosomal storage diseases?
-Tay-Sachs disease
-Niemann pick disase
-Gauchers disease
-mucopolysaccharidoses
what are the glycogen storage diseases?
-von Gierkes disease
-McArdle syndrome
-Pompe disease
an example of an X-linked DOMINANT disorder is?
vitamin D resistant rickets
this group of disorders is caused by mutations in lysosomal enzyme proteins. they are autosomal recessive. what type of disease are thse?
lysosomal storage diseases
what disease has an incidece of 1:3000 US Jews (1:30 ashkenazi Jews are carriers)?
Tay-Sach Disease
In what disease the CNS target the organs?
Tay-Sachs.
what type of gangliosides are stored extensively in the CNS in tay-sachs?
GM2
what enzyme deficiency occurs in Tay-Sachs? and what does it do?
deficiency of hexosaminidase A prevents degradation of GM2
infants develop severe mental retardation, blindness and severe neurologic dysfunction with death occuring at 2-3 yrs of age in what disease?
Tay Sach
diagnosis of tay sachs is determining hte serum level of what? and is prenatal biochemical testing possible?
hexosaminidase A level.
Yes.
Niemann-Pick disease has an accumulation of what in what 2 places?
sphingomyelin or cholerserol in phagocytic cells and sometimes CNS
which type of neimann pick disease accounts for 75-80% of cases?
type A and B
what enzyme deficiency is seen in Neimann Picks?
deficiency of acid sphingomyelinase = prevents conversion of sphingomyelin to ceramide & phosphorylcholine. excess sphingomyelin accumulates.
which type of Neimann picks is the most common?
type A. 85%.
what is the most severely affected organs of type A in neimann picks disease?
spleen, liver, BM, LN, lungs leading to severe VISCEROMEGALY. also the entire CNS is involved.
Death in Neimann Pick occurs at what age? This is similar to what other recessive mendelian disorder?
3 yrs.
Tay Sach
Type B Neimann Pick affects which organs particularly?
spleen and liver
CNS is affected in which type of neimann pick?
only A. so, now MR in type B.
diagnosis of niemann pick disease is testing sphingomyelinase activity of what type of cells? or you could culture what instead?
WBC.
Fibroblasts.
-carrier state can also be determined
in gauchers disease, what organ is primarily involved?
spleeeeeeeen
what enzyme is deficient in Gauchers disease? what does it do?
glucosylceramidase = needed to cleave glucose resideu form ceraminde
what accumulates in phagocytic cells in Gauchers disease? and what type of cells do these form? what does the cytoplasm look like?
glucosyceramides accumulate forming GAUCHERS CELLS = large cells having "wrinnkled tissue paper" cytoplasm.
what is pathognomic in Gaucher's disease?
Gaucher cells = cytoplasm looks like wrinkled tissue paper
Which is the worst type of Gaucher's disease and it manifests at what age? is there CNS involvement?
Type II: severe CNS involvement, manifests at 6 yrs.
which type of gaucher's disease occurs 99% of the time? what does it affect? is there CNS involvement?
type I. affects bone, liver, spleen. NO CNS invovement.
what is the juvenile form involving CNS and viscera of Gacher's disase? it's mild and runs an intermediate course.
type III
rate CNS involvment severity in tach sachs, neimen pick and Gauchers. which is MOST severe?
Type II Gauchers > taysach & neimenn pick
diagnosis of Gaucher's is confirmed by testing glucosylceramindase levels in what type of cells? also what type of cells can you culture?
WBC
fibroblast
-heterozygotes can be detected
In Hurler's syndrome, gingival enlargembt is seen due to storace disease. this is an example of what diseases?
Mucopolysaccharidoses = ground substances
what is the disease of 1:25,000 incidence that affects ground substances?
mucopolysaccharidoses
what disease is characterized by abnormal degradation and accumulation of mucopolysaccharides in tissue?
mucopolysaccharidoses.
ground subaces accumulated in mucopolysacchardoses are ?
-dermatan sulfate
-heparan sulfate
-keratin sulfate
-sometimes chondroitin sulfate
clinical findings of mucopolysacchardoses ----which organs are involved and how is this like Galactosemia?
organs: liver, spleen, heart, blood vessels.

-also cataracts are involved = galactosemia the same.
a rare disease with -MR, joint stiffness and course facial features present is ?
mucopolysaccharidoses
what stroage diseases have an incidence of 1:50,000
glycogen storage
a glycogen storage disease that has a ______ form is missing an enzyme from the liver. we see hepatomegaly bc glycogen is being stored in liver and also hypoglycemia. what disease?
hepatic form
what glycogen sotrage disease of hepatic form has the accumulation of G6P? what enzyme is deficient?
Von Gierke disease
glucose 6 phosphatase
muscle cramps, reduced muscle phosphrylace, reduce production of lactate following exercise, muscle weakness. . . can be seen in what disease? and what specific component is being stored.
McArdle syndrome.
glycogen
Lion's theory says that only 1 X is active in females. barbodies are involved. T/F
T
who is the most likely to express an x linked mendelian disorder>?
heterozygous male = has defec on one x chromosome and the Y can't helpt him out
dominant = male and female affected.
recessive: all males affected. hetero females are asymp carriers. T/F?
T
a miscellaneous type of glycogen storage disease that has generalized glycogenosis resutling form lysosomal glucosidase (acid maltase) deficiency is?
Pompes disease
what enzyme is deficient in Pompe's disease
glucosidase (acid maltase) deficiency
major findings of hepatomgealy, cardiomegaly, skeletal muscle glycogen deposits and glucosidase (acid maltase) deficiency is?
pompes disease
what disease can be a glycogen storage disease and a lysosomal stoarge disease?
pompe's disease
what type of disorders are these?
-hemophilia A & B
-Glucose-6-P dehydrogenase deficiency
-Agammaglobulinemia
-Duchenne & Becker muscle dystropies
X linked recessive disorders
a variable mendelian mode of transmission disease of stretch skin is?
Ehlers Danlos syndrome
what disease has pathognomic of stretchy skin?
ehlers Danlos syndrome
what deisease is common enough that you may actually see it on clinic? it's incidence is 1:5,000 to 1:10,000
ehler danlos
whats the diff btw ehler danlos and marfans?
ehlre danlos = weak CT
marfan = collagen fibers strcuturally normal, but fragment easily due to mutation in FBN1
circus man with stretchy skin can be seen in what disase?
EDS =ehlre danlos syndrome
in EDS what enzyme deficiency do we see?
def in lysyl hydroxylase = cause decreased hydroxylation of type I and III collagen, preventing normal cross linking.
-weakness of blood vessels and bowel wall.
hyperextensible skin showing extraordinary stretchyness but extremely fragile and vulnerable to trauma, hypermoile joints, =
EDS
in EDS you can see
-rubpture of large arteris due to vascular fragility
-rupture of colon
-rupture of cornea & retinal detachment
-diaphragmatic hernia
T/F
T
what ist he most common cause of FAMILIAL retardation?
fragile X syndrome
what is the most common cause of GENETIC retardation?
down syndrome
Fragile X syndrome can be mendelian OR cytogenic disorders. t/f?
t
a single-gene disorder with atypical patterns of inheritance is?
fragile X syndrome
there is a breakage of X chromosome and the reconnection is not done correctly in what?
fragile X syndrome
a mutation in what gene is associated with long repeating sequences of 3 nucleotides. normall = this pattern of inheritance expressed in males normally and asymptomatic in females, but not in this disease
fragile x syndrome
mental retardation = worse in fragile x syndrome or down syndrome?
fragile x
long face, large mandible, large everted ears, large testicles, males generally affected, 20% males with defect are normal carriers and may pass to grandchildren, 50% female carriers have MR but not as severe as males in what disease?
fragile X
in fragile X, who is mostly affected.
MALES
a risk threshold = a given number of mutant genes ust be inherited for the disease to be expressed. after threwhold is attained, severeity of disease is proprtional to number of genes with mutations can be seen in disorders with what type of inheritance?
multifactorial
first degree relatives of an affected invidual have a ____% risk of also developing the disease in multifactorail inheretance diseases. and frequency for concordance (whether or not htey both express the disease) in identical twins is about _____% vs mendelian which is 100%
207% risk
20-40% in twins
risk of recurrence of hte phenoytpic abnormality in susequent preganancies depends on the outcome of previous pregnancies. mom to baby = 50% chance. T/F
False = depesnds on previous pregnancies. diff than mendalian.
what are examples of disorders transmitted by multifactorail inheritance?
-diabetes mellitus
-hypertension
-gout
diabetes mellitus
hypertension
gout
these are examples of disorders transmitted by what type of inheritance
multifactorial
what multifactoral inheritance disorder causes arthritis?
gout
diagnosis of cytogenic diorders is based on identification of what 2 types of abnormalities in the chromosomes?
1. numerical
2. structural
chromosome analysis is perfomred by various methods of _________. what stain is widely used as the G Banding technique?
Karytyping
Giemsa stain
Karytypes can be performed on children/adults by culturing what type of cell? and where is it from?
Lymphocytes.
=peripheral blood
Karytypes can be performed on infants by culturing what type of cell? and where is it from?
fetal fibroblast
=aminotic fluid or placental sampling
the picture of chromosome in metaphase is known as
karyotype
what is the karyotype?
a picture of chromosome in metaphase
whats the karyotype of males?
46,XY
karyotype of female?
46,XX
karyotpyic notation = first you have the # of chromosomes and hten the sex profile. T/F
T
Chromosome abberations include 2 types of abnormalities
structural and numeric
numeric abnormalities = aneuploidy = def is?
any number of chromosomes that is not an exact multiple of n
any number of chromosomes that is not an exact multiple of n is?
aneuploidy
defined as 2 or more karyotypic populations of cells in the same individual. occurs more commoinly involving the sex chromosomes ?
MOSAICISM
mosaicism is a good thing bc it lessnes the severity of the cytogenic disorder bc you will at least have some normal cells. T/F
T
(n+1), (n-1), (2n+1) , (2n -1) = example of?
aneuploidy
3n, 4n, 5n = example of
polyploid.
exact duplicates of hte euplid/haplid number
diploid = normal human somatic cells
euploid = exact haploid number (gametes)
T/F
T
what are the 5 diff structural abnormalities?
1. translocation
2. isochormosomes
3. deletion
4. inversion
5. ring chromosomes
Define:
1. translocation
2. isochormosomes
3. deletion
4. inversion
5. ring chromosomes
1. translocation = segment of one chromosome is transferred to another chromosome.
2. isochormosomes: centromere divides transversely so that the 2 short arms are paired and the 2 long arms are paired = divides along wrong axis
3. deletion: loss of a protion of chromosome
4. inversion: one chromosome breaks, then the broekn segment makes a complete turn around and reattch to the origical chrosome: 2 types = para and peri
5. ring chromosomes = deletions occur at both ends of a single chromosme and damage ends fuse
what are the 2 types of translocation?
1. balanced reciprocal translocation = fragments are exchanged btwn 2 chromosomes and NO genetic material is llost.
2. Robertsonian translocation or CENTRIC FUSION = reciprocal translocation that always occurs btw 2 acrocentric cromosomes = tiny up arms are LOST
two types of INVERSIONS (stand on head, upside down! no loss but sequence affects function) are?
-paracentric = both breaks on DOWNside, define by banding patterns
-pericentric = reattaches to wrong side after breaking.
LOSS of chromosomal material is more severe than Exess of genetic material. T/F
T
autosomes are MORE severe than sex chromosomes.T
T
so a LOSS of AUTOSOMES is more severe than a GAIN of SEX chromosome
T
X is more severe than Y
T
most cytogenic disroders arise de novo= hereditary but not familial. parents are not affected, brand new, abnormality in gametes. T/F
T
Cytogenic defects involving autosomes: list 3
trisomy 21 = downs syndrome
trisomy 18 = edwards syndrome
trisomy 13 =patau syndrome
Trisomy 21 incidence is?
1:700 live births
karyotype of trisomy 21 is
47,XX+21 or 47,XY+21
95% of trisomies have the extra #21 chromosome coming from who?
mom
1:1,550 live births from moms <20 yrs.
vs
1:25 live births from moms that are > how old?
45 yrs. risk increases iwth age
4% of trisomy 21 are due to what?
translocation
ex 46, XX, der(14;21)(q10;q10),+21
1% of trisomy 21 are due to what
mosaics.
46,XX/47,XX+21
clinical features of trisomy 21 are?
-mental retardation (mild to mdoerate)
-flat facial profile
-epicanthal folds
-small maxilla
-horizontal palmar crease = semian crease = one crease only
-hypothyroidism
-hypotonia = flobby
-gaps btwn toes
in 40% of all trisomy we see congenital heart defects, what is the most common?
atrial septal defect = hole btw L & R
Edward crossed fingers rocked on his horse =
crossed fingers = 4th over 3rd = abnormal as opposed to normal. rocker bottom feet. horse shoe kidney. small jaw.
karytype of trisomy 18 is
-due to?
47, XY,+18 or 47,XX,+18
due to translocation. can be mosaics
trisomy 13 is also called what?
karyotype is?
-symptoms?
Patau
47,XX,+13 or 47,XY,+13
polydactyl, cleft lip/palate, abnormal ears, small head,
cytogenic disorders involving sex chromosomes are? 2 of them
klinefelter syndrome
turners syndrome
incidence of kleinfelter syndrome is?
common or not common?
1:1,000 live MALE births
fairly common
what is the etiology of kleinfelter?
excess nunber of sex chromosomes
2 or >2Xs
1 or >1Ys
karyotype of Klienfelter
47,XXY
or
mosaic: 46,XY/47,XXY or 47,XXY/48,XXXY
clinical features of kleinfelter are?
male hypogonadims,
small testes,
low serum testosterone level
gynecomatisa = man boobs
elongated body appeance
-reduce hair
-mild decreased intelligence = NOT MENTAL RETARDATION. bc increase in X = decrease intelligence
in kleinefelter syndrome do you see MR?
no, it's just decreased intelligence
small testes, elongated body appearance, gynecomastia, mild intelligence =
Kleinfelter
turner syndrome incidence /why is this number skewed?
and karyotyope
1:3000 LIVE female births (common in abordted fetus) this number is skewed bc it induces still births.
45,X or 45,XO
which disease has only ONE sex chromosome.
and what is it?
Turners
X
can there be variants in turners syndome?
yes.
mosaic 46,XX/45,X
isochrosome 46,X,i(Xq)
deletions 46,XXq- or 46,XXp-
clinical features of turners include?
-short stature
-webbed neck, lower posterior hair line
-board shield chest
-streak ovaries
-pigeon shoulders
-no puberty
-coarctation of aorta
-distinctly infertile, no eggs :(
distinctly inferile, webbed neck, low posterior hair line. give karyotpe and incidence
turners
45,X
1:3000 LIVE female births
gynecomatisa, elongated arms, small testes, hypogonadism.
give karytype
and incidence
Kleine felters
47,XXY
mosaic: 46,Xy/47,XXY or
47,XXY/48,XXXY
1:1,000 live male births
mental retadation, hypotonia, gaps btwn toes, atrial septal defects, big tongue, seminan crease.
give karyotype
give incidence
down's syndrome
47,XX,+21 or 47,XY, +21
1:700 live births
crossed fingers, small jaw, horse shoe kidney, MR, failure to thrive, prominent occiput = part of head is small and other side is big
karyotype
incidnce
edwards =trisomy 18
47,XY,+18 or 47,XX,+18
1:8,000
trisomy 13
incidence and karytype
1:15,000
47,XX,+13 or 47,XY,+13