4: Endocrine genetics Flashcards
Endocrine diseases have a ___ component.
genetic component
What are two general types of genetic disease?
Monogenic (caused by one gene)
Polygenic (caused by several genes + probably environment)
What are six modes of inheritance of monogenic disorders?
Autosomal dom
Autosomal recessive
X-linked dom and recessive
Y-linked
Mitochondrial
linkage studies for monogenic
What is a GWAS?
Genome-wide association study
used to identify mutations responsible for polygenic disease
Mendelian diseases tend to have ___ penetrance and ___ frequency.
Polygenic diseases tend to have ___ penetrance and __ frequency.
Mendelian - high penetrance, low frequency
Polygenic - low penetrance, high frequency
What are the two most understood monogenic endocrine syndromes?
MEN1
MEN2
MEN1 = 3 Ps (pituitary, parathyroid, pancreas)
MEN2A = parathyroid, medullary thyroid cancer, phaeo
MEN2B = mucosal neuromas, marfanoid appearance, medullary thyroid cancer, phaeo
Mutation in which gene causes MEN1?
MEN1 gene
Mutation in which gene causes MEN2?
RET gene
men1 = tumour suppressor gene, one copy
then “second hit” - environmental factor switches off second tumour suppressor gene, leading to tumour genesis
MEN1 - inactivation of tumour suppressor
MEN2 - activation of 1 oncogene
What disease tends to cause the 50% early mortality seen in MEN1 patients?
Malignant pancreatic tumours
As most patients with MEN2 will develop a medullary thyroid cancer, what treatment is carried out prophylactically?
Thyroidectomy
Carney Complex:
cushing’s disease
acromegaly
thyroid cancer
