Autosomal dominant Flashcards
rare when a _______ dominant mutation causing disease
homozygous dominant
AA
example of complete penetrance
achondroplasia
achondroplasia is autosomal _____
dominant
de novo mutation
mutations that occur in the egg or sperm or immediately after fertilzation
de novo mutations would explain
autosomal dominant disorder seen in children without affected parents
clinical achondroplasia
- short
- rhizomelic limb shortening
- short fingers
- genu varum
- trident hands
- large/frontal bossing
- midfacial retrusion
- small foramen magnum/ craniocervical instability
achondroplasia is lethal in
homozygous dominant state
achondroplasia gene
FGFR3
fibroblast growth factor receptor 3
achondroplasia gene funct
regulates bone growth by limiting the formation of bone from cartilage
achondroplasia chrom
4p16.3
nucleotide 1138
achondroplasia mutation function
increases the activity of protein interfering with skeletal development
____ has highest new mutation rate known in man
Nucleotide 1138 of FGFR3 gene
Pure dominant
Homozygotes and Heterozygotes are both equally affected
incompletely dominant
homozygotes are affected most severely
reduced penetrance
- retinoblastoma
- BRCA mutation
- huntongton’s disease
variable expressivity examples
Neurofibromatosis type 1
osteoogenesis imperfect type 1
Neurofibromatosis type 1
new mutation rate
50%
Neurofibromatosis type 1
clinical
cafe au lair spots neurofibromas plexiform neurofibroma freckling in axilla optic glioma lisch nodule osseous lesions
Neurofibromatosis type 1
mutation
NF1
neurofibromin tumor suppressor gene
loss of function
Neurofibromatosis type 1
chromosome
17q11.2
locus heterogeneity
mutation in more than one locus causing same clinical condition
locus heterogeniety example
autosomal dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease
new mutation rate
5%
Autosomal dominant polycystic kidney disease
clinical
- bilateral renal cysts
- cysts in other organs
- vascular abnormalities
- end stage renal disease
Autosomal dominant polycystic kidney disease
mutation
PKD1 chromosome 16p13.3
PKD2 chromosome 4q22.1
polycystin 1 and 2
produces truncated protein
familial hypercholesterolemia
new mutation rate
very low
familial hypercholesterolemia
clinical manifestations
high cholesterol
high LDL levels
xanthomas
premature coronary artery disease and death
familial hypercholesterolemia
mutations
- LDLK
- APOB
- PCSK9
trinucleotide repeat disorders
- expansion of segment of DNA consisting of 3 or more nucleotides
- CAG
- slipped mispairings
- anticipation
- parental transmission bias
- AD, AR nd X-linked transmission
slipped mispairing
- mispairings of bases in regions of repetitive DNA replications coupled with inadequate DNA repair systems
- as the repeat grows longer, the probability of subsequent mispairings increases
anticipation
severity and onset of diseases increases in next generation
parental transmission bias
trinucleotide expansion more prone to occur in gametogenesis of male or female
Huntington’s disease:
- autosomal dominant
- trinucleotide repeat disorder (CAG)
- anticipation
- paternal transmission
Huntington’s disease
clinical
progressive neuronal degeneration causing motor cognitive and psychiatric distrubences
onset 35-44
death 15 years after onset
Huntington’s disease
gene
HTT
Huntington’s disease protein
huntingtin
Huntington’s disease chromosome
4p16.3
