genetics Flashcards
what does monogenic mean
one gene
what does polygenic mean
multiple genes
what line is a mitochondrial genome passed through
the maternal line
from mothers
what is an indel
small insertions and deletions
what can small insertions and deletions result in
- in frame indels
- out of frame indels
- loss of function
benefits of genetic testing
- benefit for patient
- benefit for first degree relatives
- academic/research
- future clinical benefits
how do you identify those with a hereditary endocrine disease
- history and family history
- examination
- young age of onset
- tumour multiplicity
- pathognomonic clinical features
where can MEN1 cause tumours
3Ps
- parathyroid
- pituitary
- enteropancreatic
- gastric
- bronchial
clinical features of MEN1
- primary hyperthyroidism
- pancreatic neuroendocrine tumours
- pituitary adenomas
is MEN1 dominant or recessive
dominant
why is managing MEN1 difficult
- lack of genotype-phenotype correlation
- variable age-related penetrance
- inability to predict disease course
- asynchronous/synchronous development of multiple tumours
- lack of specific therapies to MEN1
is MEN2 dominant or recessive
dominant
where does MEN2a cause tumours
medullar thyroid cancer in association with phaechromocytoma and parathyroid tumours
what do MEN2 mutations result in
activation of receptor tyrosine kinase
what are the two forms of MEN2
MEN2A
MEN2B
what does MEN2B cause
medullary thyroid cancer in association with marfanoid habitus, mucosal neuromas, medullated corneal fibres, intestinal autonomic ganglion dysfunction
what is the first manifestation in MEN2
medullary thyroid cancer
signs and symptoms of MTC
- neck mass
- diarrhoea and flushing
- ectopic ACTH and Cushing
investigation for MTC
neck USS and fine needle aspiration
-measuring basal serum calcitonin
management for MTC
surgery
potential thyroidectomy
clinical manifestations of VHL mutation
- CNS
- retinal haemangioblastoma
- phaeochromocytoma
is VHL dominant or recessive
dominant
what does a VHL mutation do
leads to accumulation of HIF proteins and stimulation of cellular proliferation
neurofibromatosis type 1 is caused by a mutation in which gene
NF1 gene
clinical findings in neurofibromatosis type 1
- axillary freckling
- cafe-au-lait patches
- neurofibromas
- optic gliomas
- scoliosis
what gene is the mutation in that causes carney complex
PRKAR1A
what happens genetically in carney complex
- the mutation causes defective regulatory subunit
- then aberrant PKA signalling
- then uncontrolled proliferation
