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71 Cards in this Set
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whats a robertsonian translocation |
recriprocal translocation at the centromere of 2 acrocentric chromosomes (centromere at the end) so you get a long and short chromosome
can cause redundant DNA parent is normal, but the offspring is affected. often seen in DS |
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whats an isochromosome
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when a chromosome breaks at the centromere and you get connected P and connected q's
common in turners |
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• Ms. PAULA NOVAK (mother of 4 y/o Seth):
• Seth had open‐heart surgery in 2007, missed his one‐year cardiology follow‐up. Seth has missed appointments for eye exams, thyroid exams, ENT visits to replace tubes in his ears, genetic doctor appointments to track his growth and development, fittings for his orthotics, and very importantly ‐ because Seth is still nonverbal ‐ visits to his speech therapist. Dx? 20 |
heart problems- endocardial coushin development
eye exams thyroid Ears Orthotics non verbal dx: DOWNS SYNDROME (DS) |
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DS clinical
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trisomy 21- maternal nondisjunction
most common cause of mental retardation- inability to develop advanced cong strategies and processess 1. facial features- epicanthic folds, brachycephaly (short AP head), 2. intestinal stenosis, hirshprungs, esophageal atresia, 3. umbilical hernia 4. eyes: keratoconus, brushfield spots, cataracts increased risk 5. large tongue, small hands/feet, short. wide space bten toes 6. hypotonia |
trisomy 21
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what is the list of types of chromosome defects seen in DS, what is the associated phenotype
what type might be inherited, describe the chromosome defect |
1. nondisjunction in mom: related to maternal age
2. robertsonian translocation: NOT related to maternal age. same phenotype as trisomy 21 3. other translocation: 9p trisomy t11:22 4. 1% are mosiacs: MILD phenotype. also NOT related to maternal age |
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in what disease is a prominent epicanthic fold present
in what disease is a simian crease present |
DS- its the fold of skin near the inner eyelid
DS- the line on the hand |
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we know the classics trisomy 21, facies, and retardation with DS, what else goes with it
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1. intestinal stenosis, hirshprungs, esophageal atresia
2. umbilical hernia 3. eyes- heratoconus, brushfield spots, cataracts 4. large tongue 5. short, small hands/feet 6. heart disease bc of endocardial cushion failure. venous flow is affectted, ASD, VSD 7. increased risk of ALL and abnormal T cell responses 6. hypotonia, simian crease, wide space btwn 1/2 toe |
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ok so you are doing an exam and you see a cone like cornea, what is it called, what disease is it assocaited with, why does it occur
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keratoconua
seen in ds its when superoxide dismutase is absent and you get the sclera building up |
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why do pts with downs syndrome have premature death
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cardiac complications- its super common. its an endocardial coushin problem.
ASD VSD |
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ALL is more common in what disease
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downs syndrome
**also abnormal T cells, see pulm/ear infectins, AI disease, thyroid disease, celiac, AD |
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leukemia, abnormal T cell, AD, AI thyroid, celiac are all more common in what group
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DS
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lets put downs all on one page
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1. growth failure, mental retardation, flat head, brachycephaly, abundant neck skin
3. congenital heart disease, AV septum 3. intestinal stenosis, megacolon, umbilical hernia 4. karyotype: triosomy 21, translocations, mosiac 5. AD age 40 6. slanted eyes, epicanthal fold, brushfield spots, keratoconus, flat face, dysplastic ears, protuding wrinkled tongue, 7. short broad hands, simian crease, wide gap in toes 8. ALL |
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whats the prenatal screen for DS
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1. AFP decreased
2. PAPP-A decreased 3. b hGC increased 4. Inhibin A increased *nuchal lutency, cardiac and intestinal abnormality |
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whats the possible outcome
AFP low, hCG high, inhibin A increased, PAPPA low. nuchal lucency |
DS
**can also see cardiac and intestinal problems **dx by doing chromosomes on amniocentesis |
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what are the features of trisomy 18, whats the pathogenesis
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Edwards Syndrome: non disjunction or mosiac
more common in older mommas rocker bottom feet, long overlapping fingers, congenital heart defect small mouth, low set ears |
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what is Edwards Syndrome: i
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trisomy 18, its a low set ears, small mouth, prominent occuput
1. first finger is long 2. horeshoe kidney 3. IUGR 4. congenital heart disease 5. rocker bottom feet **BAD prognosis, most die in a year *caused by non disjunction or mosiacs |
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a baby is born to a mom who is 45 and the babe is small, has a small head and mouth with a large occuput, the baby has low set ears and short neck. you can see that the feet are rocker bottom adn the fingers overlap. what might you expect the heart to be like.
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Edwards syndrome, trisomy 18
cardiac defects, limited hip abduciton, horse shoe kidney |
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rocker bottom feet is seen with...
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trosomy 18, edwards
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whats is patau syndrome
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trisomy 13- increased occurence with increases AMA. result of non disjunction or mosaiacs (same as edwards-18)
really bad, most die before 1 mo. IUGR clef lip, clef palate |
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what disease did that baby have that dr devine did the autopsy on
what did they look like |
patau- trisomy 13.
**its a clef palate, clef lip, polydactyly, cyclopea |
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what is the trisomy that is associated with clef lip/palate and polydactyly, it has renal defects and congenital heart disease, also has rocker bottom feet
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patau-
**both edwards and patau have rocker bottom feel also can have cyclopea |
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cyclopea is associated with what trisomy
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13- clef lip/palate, heart, polydactyly
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what are hte features of 22q11 deletion syndrome
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DiGeroge:
conotruncal outflow defects cleft lip/palate developmental delay **T box gene deletion psychiatric disorder- ADD, bipolar, schzo |
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whats cri du chat
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deletion
cry of the cat 5p- dletion |
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whats the chromosome of DiGeorge
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22q11 deletion
**thymic hyposplasi with T cell deficit **hypoplasia of parathyroid --> hypocalcemia *8heart defects, **facial deformity TBOX gene deletion |
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TBOX gene deletion is associated with what
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22q11
3/4 pharyngeal pouch |
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5p- deletion
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cri du chat
**cry of the cat, its a kitten cry -small head, no mm tone, severe retardation, round face, low birth weight, failure to thrive |
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what is the disorder with the round face, retardation, low mm tone, small head, and failure to thrive. it is a 5p- deletion
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cat cry- cri du chat
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name 6 deletion syndromes
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1. DiGeorge: 22q11
2. Wilms 11p- 3. retinoblastoma: 13q- 4. Cri du chat: 5p- 5 Prader Willi 15 deletion 6. Angleman: q11p13 |
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why are all females mosiacs
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lyon hypothesis- one x is inactivated randomly, can be from the mom or dad.
XIST gene inactivates the x by coating iy in non coding RNA |
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what determines male sex
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SRY on Y chromosome
**can be translocated to an x so its an XX male |
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what sx are common in ppl as they accumulate more and more x chromosomes
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get cognitive impairment
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when are sex abnormalities ussually discovered
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puberty
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what are the clinical features of kleinfelter syndrome
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male hypogonadism, XXY- maternal/paternal nondisjunction
female fat- hips, breasts tall- long legs small penis small testicle low IQ, not retarded Pathogenesis of symptoms ‐ androgen receptor, located on X inactivated ‐‐ CAG trinucleotide repeat polymorphism *dx AFTER puberty |
w
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what is the most common kayrotype for kleinfelters
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XXY- paternal/maternal non disjunction
Pathogenesis of symptoms ‐ androgen receptor, located on X inactivated ‐‐ CAG trinucleotide repeat polymorphism |
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what are some complications associated with kleinfelters
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infertility
extragonadal germ cell tumors breast CA risk Pathogenesis of symptoms ‐ androgen receptor, located on X inactivated ‐‐ CAG trinucleotide repeat polymorphism |
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what are the consequences of XYY
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pretty common, normal phenotype, tall, acne, normal intelligence
**contrast with kelinfelter XXY where you are a little low IQ |
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what are the labs with kleinfelters
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elevated FSH
low testosterone |
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your male pt is really tall and you think he should play b ball but hes not very athletic. he has a hard time finding pants that are long enough. his FSH is increased and he is conserned about his reast buds.
what are his genetics what is he at risk for |
xxy- kleinfelters
infertile, extragonadal germ tumors, breast CA |
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An 18 y/o mother delivered a stillborn female
fetus of 23 weeks gestational age. The fetus had bilateral cervical cystic hygromas and massive hydrops. The distraught mother insisted upon knowing why her baby died. At autopsy, the fetus had coarctation of the aorta, dysgenesis of the ovaries, and a horseshoe kidney. Tissue obtained at autopsy had a 45,X karyotype. |
turnershypogonadism in female (male hypogonadism is kleinfelter)
*most cases are non viable |
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what are the features of turners
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fetal loss is common- hydrops
peripheral lymphedema at birth webbed neck- cystic hygroma, bc of lymphedema short |
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what are hte kinds of chromosome defect seen in turners
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45 XO- many are mosiacs
structural prblm with X to make partial X monosomy mosiacs |
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this baby girl is born to a mom and the baby had edema in hands/feet. webbed neck. what might she have, what are some complications
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turners
wide chest with widely spaced nipples, normal intelligence moles coarctation cubital valgus- wide carry angle of arms |
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moles, wide carry angle, coartation and broad chest are all asscoated with what? what else will this girl have
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turners syndrome
ovarian streak, increased AI disease, Thyroid autoab --> hypothyroid |
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what thyroid is associated with turners
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increased risk of AI disease
hypothyroid from autoAB **will also have icnreased risk of celiac disease. simliar to DS |
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what disease has a short 4th metacarple
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turners
knuckle knuckle dimple knuckle |
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webbed neck, small 4th metacarple, moles, wide carry angle
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turners
streak ovary, increased risk of AI thyroiditis coarctation chest shield, wide spaced nipples peripheral edema at birth |
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whats the girly girl reason blond jokes exist
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multi X female
phenotype is normal but remember what we said about XX, any more than 2 and cognition starts to nose dive |
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genetic gex
gonadal sex ductal sex phenotypic sex sexual ambiguity |
genetic gex: y or no Y
gonadal sex: testes, ovary ductal sex: mullerian (women) wolffian (men) phenotypic sex: what does it look like, external sexual ambiguity: disagreement |
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what defines a true hermaphodite, what are some causes
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1. ovaries and testes BOTH
usually a 46 XX with SRY present 47XXY |
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chimera
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a single person with cells from 2 zygotes
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female pseudohermaphoditism
whats teh most common cause, what are hte features |
XX with male external genitalia. ovaries are present
**excessive/inappropriate exposure to androgens in early gestation -adrenal hyperplasia -exogenous angrogens given during preggo |
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if someone has ovaries but their external genitalia is confused what might the problem be
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female pseudohermaphodite (XX) who was exposed to andorgens in utero. could have been from mom taking them exogenously or adrenal hyperplasia
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what is a male pseudohermaphodite
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genetic male (XY) who has female/ambigious external genitalia.
caused by androgen insensitivity syndrome or testicular feminization |
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female and male pseudohermaphodites. what do they look like and why
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Female pseudohermaphodite: XX, ovaries are present but external genitalia are confused bc in utero they were exposed to too much andorgen bc of 1. adrenal hyperplasia or 2. mom took androgens when preggo
2. male: XY with testes but feminization/breast, bc of androgen insensitivity (testicular feminization) |
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congenital adrenal hyperplasia in a baby girl will cause what.
internal sex external sex |
adrenal hyperplasia --> increased androgen,
genetic female (XX) w/ovaries external genitalia is male FEMALE pseudohermaphodite |
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a Y chromosome baby has testes and female external genitalia. what is this called, what is the cause
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male pseudohermaphodite
**defective Androgen receptor, testicular feminization |
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• A 19 y/o woman c/o primary amenorrhea.
• The patient had normal breast development and normal female external genitalia, but she had no pubic or axillary hair, and the vagina was short and ended in a blind pouch. • Abdominal exploration revealed no uterus, but testes were present which were resected. They contained immature small numbers of Sertoli cells and germ cells and moderate Leydig cells. |
male pseudohermathodite
testicular feminization bc of androgen R insensitivity |
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trinucleotide repeat mutations. what are some examples
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long repeats of 3 nucleotides. this makes the DNA unstable and gene fx impaired
Fragile X Fredrich Ataxia Myotonic Dystrophy Huntingtons Spinocerebellar |
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what bases are involved with trinucleotide repeats
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C G
*HD, fragile X, freidch ataxia, myotonic dystrophy, spinocerebellar ataxias |
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what disease is related to trinucleotide repeat expansion in coding regions adn what are the general characterisitcs of this genetic disease
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Huntington- CAG in coding region
- gain of fx --> neurotoxicity, aggregated misfolded protein dementia, chorea |
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anticipation is common in what kind of mutations
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trinucleotide repeat expansions
ex huntingtons- CAG in coding region |
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Fragile X
1. inheritance 2. clinical 3. other associated conditions |
1 trinucleotide repeate more common in boys. FMR1 gene mutation. CGG repeate makes X look fragile
2. 2 most common cause of inherited mental retardation (DS is 1) LONG face, macro-orchidism. MVP, large ears, hyperextendable joints |
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A seven year old girl is seen by the
school counselor due to failure to make expected progress in the first grade despite being held back a year. She has particular difficulty with math concepts and sequential reasoning. Testing reveals cognitive impairment. She is referred to a physician for medical evaluation. History reveals that this child is the oldest of three, the product of a normal pregnancy and delivery. Growth has been average for age. She has been seen regularly for immunizations and well‐child checkups. There was some indication of developmental delay. She started first grade at age 6 1/2 yrs. Her parents are healthy with no significant physical illnesses. Both are college graduates. The maternal grandfather was diagnosed with “atypical” Parkinson’s disease in his 60’s due to a tremor and ataxia. He did not respond to standard therapy for Parkinson’s disease. Her father has a normal brother, sister. Her mother has two normal brothers. Mother’s sister was found to have premature ovarian failure on an infertility workup. The child has two brothers. The 5 y/o developed in a timely fashion and already reads. The three year old brother has been developmentally delayed and did not walk until 20 months of age. Autism is under consideration due to behaviors that include hand flapping, hand biting and gaze aversion. The doctor orders a PCR genetic test that demonstrates an abnormality in FMR1. She recommends that the 3 y/o also be tested |
FMR1 gene associarted with fragile X
**its a disease characterized by mental retardation adn a long face. its a trinucleotide repeat expansion of CGG in untranslated genes *ovarian failure is common |
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what does mitochondrial inheritance look like
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mom transmitts to ALL children, boys do NOT transmit to ANY kids
**common disorders are MELAS and leber heriditary optic neuropathy, mitochrondrial encephalopathy |
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what is leber hereditary optic neuropathy
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progressive BL loss of central vision, variable expression.
mitochrondrial inheritance |
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MELAS
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mitochondrial encelopathy, lactic acidosis, adn stroke like episodes.
mitochondrial disorder. |
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whats the genetic defect in prader willi
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deletion inherited from the father. gemonic imprinting
**short, mental, obese, hypogonadism |
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what is genomic imprinting
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when there is selective inactivation of mom or dads allele
maternal imprinting: silences maternal allele paternal imprinting: silences paternal allele |
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what is angelman syndrome
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happy pupptet
*its when you have deletion inherited from mom. *mental retardation, laugh, ataxia |
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whats MiRNA and SiRNA
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micro RNA- small, regulatory genes, dont encode protein
fx to silence gene expression hopeful that they will be able to be used in dx and tx of disease |
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