Week 2 genetic disorders Flashcards
What is germline mosaicism?
The presence of more than one genetically distinct cell line
What is the inheritance pattern, penetrance, expressivity, frequency of de novo mutations in Marfan syndrome?
Autosomal dominant, complete penetrance, highly variable expressivity, 50% de novo
What gene is affected in NF1?
NF1, encodes neurofibromin (Ras inhibitor expressed in many types of nerve cells)
What are the signs and symptoms of NF1?
Café au lait spots, axillary/inguinal freckling, neurofibromas, Lisch nodules, tibial bowing
What gene is affected in Marfan syndrome?
FBN1, encodes fibrillin
What are the signs and symptoms of Marfan syndrome?
Dilated aortic root (essential for diagnosis), ectopia lentis, systemic features (wrist/thumb sign, scoliosis/kyphosis, reduces elbow extension, etc.)
What is the inheritance pattern and frequency of de novo mutations in Marfan syndrome?
Autosomal dominant, 25% de novo
What gene is affected in achondroplasia?
FGFR3 (fibroblast growth factor receptor 3), negative regulator of bone growth (gain of function mutation)
What is the inheritance pattern and frequency of de novo mutations in achondroplasia?
Autosomal dominant, complete penetrance, *low variable expressivity, 80% de novo
What are the signs and symptoms of achondroplasia?
Short stature, rhizomelic shortening of the limbs, macrocephaly, normal IQ, skeletal and CNS abnormalities
What is the inheritance pattern of sickle cell disease?
Autosomal recessive
What gene is affected in cystic fibrosis (CF)?
CFTR, encodes chloride channel
What is the inheritance pattern of cystic fibrosis?
Autosomal recessive
What gene is affected in incontinentia pigmenti?
NEMO
What is the inheritance pattern of incontinentia pigmenti?
X-linked dominant, fatal in males
What are the signs and symptoms of incontinentia pigmenti?
Blisters, skin redness; progresses to thickened skin, then hyperpigmentation
What is the inheritance pattern of hemophilia A?
X-linked recessive
What are the signs and symptoms of hemophilia A?
Factor VIII deficiency; inability to clot, excessive bleeding
What gene is affected in Duchenne muscular dystrophy (DMD)?
DMD, encodes fibrilin
What is the inheritance pattern of Duchenne muscular dystrophy?
X-linked recessive
What are the signs and symptoms of Duchenne muscular dystrophy?
Progressive muscle weakness, wheelchair bound by age 10, early death (35ish) from respiratory insufficiency
What is the inheritance pattern of red-green colorblindness?
X-linked recessive
