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
Huntington disease repeat
Repeat of CAG
How does parent of origin influence Huntington’s disease?
Early onset – paternal
Later onset - maternal
Mutation for Huntington’s disease occurs on the ____ gene, encoding for ______ on chromosome
HTT
Huntingtin
Chromosome 4p16.3
The expansion of glutamine may cause an altered structure or biochemical property of the protein
Huntington’s repeats normal vs abnnormal
39: full penetrance
Myotonic Dystrophy Type 1 repeat
CTG
Clinical Manifestations of Myotonic dystrophy type 1
Adult onset muscular dystrophy Progressive muscle wasting and weakness Myotonia Cataracts Cardiac conduction defects
Mutation for Myotonic dystrophy occurs on the ____ gene, encoding for ______ on chromosome
DMPK
Myotonic dystrophy protein kinase
Chromosome 19q13.3
Myotonic dystrophy repeat normal vs abnormal
5-34 normal
34-49 premutation range
>50 full mutation with 100% penetrance
Tuberous sclerosis gene mutation
TSC1 or TSC2
Tuberous Sclerosis clinical manifestation (yeah right)
Angiofibromas- benign tumor on nose
Cardiac rhabodmyoma- pediatric tumor of heart
Cortical dysplasias- neurons in brain fail to migrate properly
Hypomelanotic macules- albino spots
Lymphangioleiomyomatosis- not gonna bother
Multiple retinal nodular hamartomas- non cancerous tumors
Renal angiomyolipoma
Shagreen Patch- thickened pebbly skin
Subependymal nodule
SEGA
Ungual Fibroma- lumps near nail folds
