autosomal dominant inheritance (4 KEY FACTS)
phenotype appears in every generation, each child of an affected parent has a 50% chance of inheriting trait, male to male transition confirms, males and females equally likely to be affected
what is the cause of achondorplasia? (3)
due to mutation of the fibroblast growth factor receptor-3 gene (FGFR3), gain of function mutation, bone growth limited
what are the clinical features of achondorplasia? (5)
short stature and limbs, neurological complications-neurological exams important, macrocephaly, frontal bossing, hydrocephalus
etiology of achondorplasia (2)
80% new mutations (advanced parental age), complete penetrance
what are some of the clinical signs of Marfan syndrome? (5)
tall statures with long limbs and digits, anterior chest deformity, opthalmological problems, mitral valve prolapse, aortic dissections
what is the cause of Marfan syndrome? (2)
mutation of fibrillin-1 (FBN1) gene, dominant negative effect
what is a dominant negative mutation?
mutant gene codes for a mutant protein that binds to and inactivates a protein complex
what is a dominant gain of function mutation?
mutant gene codes for mutant protein that has a new functions or altered deleterious functions
management/treatment of Marfan syndrome (3)
early diagnosis, control cardiac problems with beta blockers, avoid contact sports
etiology of Marfan syndrome (3)
wide variability in expression, pleitrophy, complete penetrance
what are some of clinical signs of Huntington disease? (3)
chorea, athetosis-slow writhing movement, dementia/psychosis
etiology of Huntington disease (2)
anticipation-symptoms begin at younger age in successive generations
what is the cause of Huntington disease?
a CAG trinucleotide repeat expansion in the huntington gene
what are the clinical symptoms of neurofibromatosis 1 (4)
cafe au lait spots, neurofibromas, lisch nodules, further complications like acoustic neuromas-careful monitoring required
etiology of neurofibromatosis 1 (2)
loss of heterozygosity-somatic mutation of normal allele so affected patients have no normal NF1 gene, variability in expression
what is the cause of neurofibromatosis 1?
a mutation of neurofibrmin (NF1) gene
etiology of charcot-marie-tooth disease 1A (1)
what are some of the clinical symptoms of charcot-marie-tooth disease 1A? (4)
distal weakness, distal extremity sensory loss (joint position and vibration), areflexia, slow nerve conduction studies
what is the cause of charcot-marie-tooth disease 1A?
duplication of PMP-22 gene leads to overproduction and an overall reduced amount for myelin formation