Genetics Flashcards
Duchenne dystrophy characteristics
- X-linked
- Frameshift deletion/nonsense
- truncated/absent dystrophin protein = progressive myofiber damage
- increase CK and aldolase
What is the largest protein-coding human gene
Dystrophin gene (DMD)
- increase chance of spontaneous mutation
What does dystophin do
- helps anchor muscle fibers in skeletal/cardiac muscle
- connects intracellular cytoskeleton (actin) to transmembrane proteins alpha/beta-dystroglycan - which are connected to ECM
Loss of dystrophin causes
myonecrosis
Gowers sign can be seen in
- Duchenne (classic)
- other muscular dystrophy
- inflammatory dystrophy (polymyositis)
Duchenne weakness begins where
pelvic girdle muscles and progresses superiorly
Becker muscular dystrophy characteristics
- X-linked
- non-frameshift deletions in dystrophin gene
- gene partially functional, not truncated
- less severe than Duchenne
- adolescent/early adult onset
Deletions in dystrophin gene can cause what two dystrophies
Duchenne
Becker
Characteristics of myotonic type 1 dystrophy
- AD
- CTG trinucleotide repeat expansion in DMPK gene
- abnormal expression of myotonin protein kinase
- myotonia (difficulty releasing from handshake)
- muscle wasting
- cataracts
- testicular atrophy
- frontal balding
- arrythmia
- Cataracts
- early balding in men
- gonadal atrophy
- can’t release from handshake
Myotonic type 1 dystrophy
Characteristics of Rett syndrome
- almost always girls
- sporadic disorder
- MCC de novo mutation MECP2 on X chr
- onset 1-4 yrs
- regression in motor, verbal, cognitive abilities
- ataxia
- seizures
- growth failure
- hand-wringing
What happens to males with Rett syndrome
die in utero or shortly after birth
- CGG trinucleotide repeat
- XD
- long face w/protruding chin
- post-pubertal giant gonads
- large elevated ears
- MVP
Fragile X syndrome
Fragile X syndrome caused by
CGG trinucleotide repeat in FMR1 gene
- hypermethylation = decreased expression
- LOF mutation
MCC of inherited intellectual disability
2nd MCC of genetically associated mental deficiency
Fragile X syndrome
What does trinucleotide repeat expansion occur in Fragile X syndrome
oogenesis
What happens to girls with fragile X syndrome
less severe disease
- CAG trinucelotide repeat
- AD
- caudate has decreased Ach and GABA
Huntington disease
- CTG trinucleotide repeat
- AD
- cataracts
- early balding in men
- gonadal atrophy
- myotonia
Myotonic dystrophy
- AR
- GAA trinucelotide repeat
- ataxic gait
Friedreich ataxia
What are the 5 A’s of Down syndrome
- Advanced maternal age
- Atresia (duodenal)
- Atrioventricular septal defect
- Alzheimer disease (early onset)
- AML/ALL
GI manifestations of Downs syndrome
duodenal atresia
Hirschsprung disease
First trimester test for Down syndrome
- increased nuchal translucency
- hypoplastic nasal bone
- increased hCG and inhibin
Down syndrome lab in second trimester
increased hCG and inhibin A
decreased estriol and AFP
First trimester labs for Edwards and Patau
decreased hCG and PAPP-A
2nd trimester lab for Edward syndrome
hCG, inhibin A, estriol, AFP all decreased
(inhibin A might be normal)
Gi manifestation of Edwards syndrome
Meckel/malrotation
omphalocele
small jaw (micrognathia)
heart manifestation of Edwards syndrome
VSD, PDA
Edwards syndrome is d/t
meiotic nondisjunction
- error in oocyte division
- prior to ovulation and fertilization
What is seen on U/S for Edwards syndrome
fetal growth restriction
Congenital deletion of short arm of chr 5
46 XX or XY, 5p-
Cri-du-chat syndrome
Characteristics of cri-du-chat syndrome
- microcephaly
- moderate to severe intellectual disability
- high pitched cry/meowing
- epicanthal folds
- cardiac abnormalities (VSD)
Congenital microdeletion of long arm of chr 7
Williams syndrome
- Elfin facies
- intellectual disability
- hypercalcemia
- well-developed verbal skills
- extreme friendliness w/strangers
- cardiovascular problems
- renal artery stenosis
Williams syndrome
What cardiac problems seen in Williams syndrome
- supravalvular aortic stenosis
- renal artery stenosis
what 3 genetic disorders are associated with X chromosome
- Fragile X syndrome
- X-linked agammablogulinemia
- Klinefelter syndrome
What chromosome are NF1, BRCA1, and TP53 associated with
chromsome 17
