Autosomal dominant/Mitochondrial Flashcards
Achondroplasia
-caused by? on what ch?
substitution on G1138A in fibroblast growth factor receptor 3 (FGFR3) gene on ch 4p16
Paternal age effect is seen in achrondroplasia in at what age?
> 40
What is the highest known mutation rate known to man?
G1138A
Neurofibromatosis type I
cause by? on what ch?
mutation in neurofibromin (NF1) n ch 17q11
NF1 is a tumor suppressing gene
- loss in function mut.
Neurofibromatosis type I
phenotype?
cafe au lait spots neurofibromas lisch nodules freckling in axillary or inguinal area optic glioma osseous lesions
Osteogenesis Imperfecta type I
cause by? on what ch? results in?
Mut in COL1A1 gene (collagen type I alpha I) on ch 7q21
-results in reduced production of pro alpha 1 chains that reduce type I collagen production by half
Marfan’s syndrome
cause by? on what ch? results in?
mut in FBN1 gene/splicing defect in fibrillin gene on ch 15q21
-results in reduced # of microfibrils (helps things be elastic)
Polycystic kidney disease
cause by? on what ch?
mut in either:
- PKD1 on ch16p13 (85%)
- PKD2 on ch4q22 (15%)
Polycystic kidney disease
phenotype?
bilateral renal cysts
vascular abnormalities
end stage renal disease by 60 yrs in 50%
Polycystic kidney disease has locus homogeneity/heterogeneity?
heterogeneity
Hypercholesterolemia
caused by:
mutations in 3 genes:
LDLK
APOB
PC5K9
Hypercholesterolemia
phenotype
high cholesterol (>310) and LDL levels(>190)
xanthomas (cholesterol under skin)
premature coronary artery disease
What is the new mutation rate of: Achondroplasia? Neurofibromatosis Type I? Marfan's syndrome? Polycystic kidney disease? hypercholerolemia?
Ac: 80% NF: 50% M: 25% PKD: 5% HC: very low
Trinucleotide Repeat disorders are gained in which phase of development?
gametogenesis
Name that repeat! and # of repeat
Huntingtons
Myotonic dystrophy type I
Fragile X
Huntingtons: CAG > 40
Myotonic dystrophy type I: CTG > 50
Fragile X: CGG > 200
Name that mutated region!
Huntingtons
Myotonic dystrophy type I
Fragile X
Huntingtons: exon region
Myotonic dystrophy type I: 3’ region
Fragile X: 5’ UTR
Fragile X syndrome
cause by?
FMR1 gene on Xq27
Fragile X syndrome
phenotype?
dysmorphic features: large ears, long face, macroochidism Intellectual disabilities autistic behavior social anxiety, hand flapping/biting aggression
Lesh Nyhan syndrome
cause by? results in?
mut in HPRT1 gene coding for HPRT1 protein,
results in ineffective purine recycling
Duchenne Muscular dystrophy
Cause by? what ch?
premature termination of DMDXp21 gene coding for dystrophin
Hemophilia A is caused by? what ch?
Mut in factor VIII gene on chXq28
4 unique features of mitochondrial inheritance
maternal inheritance
replicative segregation
homoplasmy/heteroplasmy
threshold effect
What is the threshold effect?
too much mut mtDNA past threshold = disease phenotype
What is homoplasmy/heteroplasmy?
some mut/some norm mtDNA present and you are fine
