Autosomal Dominant disorders Flashcards
Mutation rate and penetrance of achondroplasia
80% new mutation rate
100% penetrance
Clinical manifestations of achondroplasia
Small stature Males 4’ 3” Females 4’ Rhizomelic limb shortening Short fingers Genu varum Trident hands Large head/frontal bossing Midfacial retrusion Small Foramen Magnum/Craniocervical instability
Mutation of achondroplasia is in the _____ gene which codes for ____
FGFR3
Fibroblast Growth Factor Receptor 3
achondroplasia mutation is on chromosome ______ at nucleotide ____
Chromosome 4p16.3 nucleotide 1138
Glycine to arginine missense mutations
Example of paternal age effect
Nucleotide 1138 of the FGFR3 gene has the highest new mutation rate known in man
Pure dominant vs incompletely dominant
Pure: Homozygotes and Heterozygotes are both equally affected
Incomplete: Homozygotes are affected more severely
Retinoblastoma mutation occurs at the ___ gene on chromosome ____.
RB1
13
Diagnostic criteria for Neurofibromatosis Type 1
6 or more café-au-lait spots 2 or more neurofibromas 1 plexiform neurofibroma Freckling in the axillary or inguinal area Optic glioma 2 or more Lisch Nodules Distinctive osseous lesions Affected first degree relative
Mutation for Neurofibromatosis occurs at the ____ gene on chromosome ______.
NF1 Neurofibromin- tumor suppressor gene Chromosome 17q11.2 Loss of function mutation *** Must have mutation in both genes to show phenotype
Two disease we discussed that exhibit variable expressivity
Neurofibromatosis, Marfan’s, and Osteogenesis imperfecta type 1
Clinical manifestations of osteogenesis imperfecta type 1 (4)
Multiple fractures
Mild short stature
Adult onset hearing loss
Blue sclera
Mutation for osteogenesis imperfecta occurs on the ____ gene, encoding for ______ on chromosome _____
COL1A1
Collagen type 1 alpha 1
Chromosome 7q21.3
Clinical manifestations in Marfan’s (4)
Systemic disorder of connective tissue
Ocular
Skeletal
Cardiovascular
Mutation for Marfan’s occurs on the ____ gene, encoding for ______ on chromosome
FBN1
Fibrillin- extracellular matrix protein
Chromosome 15q21.1
Mutation in the FBN1 gene is a _____ mutation that reduces the number of ____
Dominant negative mutation
severe reduction of microfibrils