193 Endocrine syndromes Flashcards
What mutation is implicated in MEN1?
a germline alteration affects one allele of the tumor suppressor menin
if the second allele is “hit” it will lead to cancer development
What mutation is implicated in MEN2?
a monoallelic gain-of-function mutation in in RET
What is penetrance vs. expressivity?
penetrance = the extent to which individuals with a genetic mutation experience the phenotype
expressivity = the degree of phenotypic expression or the spectrum
What is allelic vs. locus heterogeneity?
allelic heterogeneity = different mutations in the same gene can cause an identical or similar phenotype
locus heterogeneity = identical or highly similar phenotype may result from mutations in different genes
What is the main benefit of comprehensive sequencing technologies?
facilitates the analysis of multiple genes or the whole genome at low cost
What are the consequences of mutations in the 21 hydroxylase gene in females and in males?
major cause of congenital adrenal hyperplasia
in females: ambiguous genitalia at birth due to excess androgens in utero
in males: presents after 1-4 weeks with failure to thrive, vomiting, dehydration, hypotension, hyponatremia, hyperkalemia, shock
What are the major components of MEN1?
1) primary hyperparathyroidism
2) pituitary adenoma
3) pancreatic/duodenal tumors
What are the major components of MEN2A?
medullary thyroid cancer, primary hyperparathyroidism, pheochromocytoma, extra-endocrine manifestation
What are the major components of MEN2B?
medullary thyroid carcinoma, pheochromocytoma, intestinal ganglioneuromatosis
What pitfalls of genetic testing are associated with allelic heterogeneity?
multiple different mutations can occur in the same gene, so you need to sequence the whole gene to find the defect
What pitfalls of genetic testing are associated with locus heterogeneity?
similar disease phenotype occurs from mutations in different genes, so you need to think of different genes to test
