Gene responsible for Achrondroplasia?
FGFR3 - fibroblast growth factor receptor 3
is a tyrosine kinase receptor
chr 4p16.3 nucleotide 1138
amino acid substitution
Inhibits chondrocyte proliferation and differentiation
Classic features of an Autosomal Dominant pedigree
- disease is only passed from affected parents. (not hidden in carriers)
- affects every generation (50:50 chance of being passed on)
- affects M / F equally
pure dominant vs incompletely dominant
purely dominant: homozygous and heterozygous clinical presentations are the same
incompletely dominant: homozygotes are affected more severely
What percent of achondroplasia cases are a new mutation?
Give some examples of disease that are autosomal dominant but show reduced penetrance.
- brca mutation (breast cancer)
- huntingtons disease
different severity, onset etc of a disease in people with the same allele
Some examples of disorders of variable expressivity
neurofibromatosis type 1
van der woude
Van Der Woude syndrome?
IRF6 gene on chr1 ; haploinsufficiency –> auto. dom.
cleft lip, cleft palate, hypodontia, narrow arched palate, congenital heart disease, heart murmer, cerebral abnormalities, polythelia, ankyloglossia, adhesions btwn upper and lower gum pads, syndactyly
Neurofibromatosis type 1
50% new mutations
NF1 gene - tumor supressor gene; neurofibromin protein
auto dom, loss of function
neurofibromas, cafe au lait spots, Lisch Nodules (hamartomas of the iris), freckling in axillary or inguinal areas, optic glioma (tumor of iris)
distinctive osseous lesions, affected first degree relative