MEN Flashcards
what is the inheritance pattern of MEN1
autosomal dominant
what is the affected gene in MEN1
MEN1 gene - 11q
what kind of gene is the MEN1 gene
classic tumour suppressor
what causes MEN1 syndrome
Bi-allelic inactivation and loss of heterozygosity
where do the mutations occur in MEN1
throughout the coding region of MEN1 gene
what kind of mutation is seen in MEN1
loss of/reduced protein function
is there phenotype/genotype correlation in MEN1?
no
what are the features of MEN1
Enteropancreatic tumours
Bronchial Carcinoid
Pituitary adenoma
parathyroid hyperplasia
what are some enteropancreatic tumours seen in MEN1
gastrinoma
insulinoma
glucagonoma
VIPoma
what would some features be of a glucagonoma
migrating rash glossitis chelitis anaemia weight loss increased plasma glucagon increased glucose
what % of people will die as a result of MEN1
50%
what are the main causes of death in MEN1
malignant pancreatic neuroendocrine tumour
thymic carcinoids
what is the inheritance pattern of MEN2
autosomal dominant
what is the affected gene in MEN2
RET gene - 10q 11.2
what kind of gene is the RET gene
classic proto-oncogene
what kind of mutation is seen in MEN2
germline gain of function mutation
is there a phenotype/genotype correlation in MEN2
yes
where do the mutations occur in the RET gene
limited to specific codons
what do the mutations in MEN2 cause
affect specific cysteine residues which results in activation of receptor tyrosine kinase
what is another name for MEN2A
sipple syndrome
what are the features of MEN2A
phaeochromocytoma (may be bilateral and extra-adrenal)
medullary thyroid carcinoma (100%)
parathyroid hyperplasia
what are the features of MEN2B
phaeochromocytoma medullary thyroid carcinoma mucosal neuromas/ganglioneuromas marfanoid habitus hyperparathyroidism
what are mucosal neuromas/ganglioneuromas
bumps on lips, cheeks, tongue, epiglottis, eyelids
visible corneal nerves
in MEN2B what is the mutation almost always
activating point mutation in catalytic domain of encoded enzyme
what should be considered for treatment in MEN2
prophylactic thyroidectomy
what should people with MEN2 be screened for
phaeochromocytoma and parathyroid disease
what is a monogenetic disorder
single gene aetiology
how are monogenetic disorders studied
linkage studies
what are the 6 patterns of inheritance of monogenetic disorders
AD, AR, XLD, XLR, Y-linked, mitochondrial
what is a polygenic disorder
multiple genes
how are polygenic disorders studied
GWAS studies (genome wide assoc. study - looking at large populations)
does WGS or WES give more complex info
WGS
is WGS or WES cheaper
WES
will WGS or WES see non-coding changes
WGS
is WGS or WES more targeted approach
WES
what is the syndrome: axillary freckling cafe-au-lait patches neurofibromas optic gliomas scoliosis learning difficulties iris hamartomas phaeochromocytoma
neurofibromatosis type 1
what is the inheritance pattern of NF1
autosomal dominant
what is the syndrome:
bilateral acoustic neuromas
multiple intracranial schwannomas, meningiomas and ependymomas
neurofibromatosis type 2
what is the inheritance of neurofibromatosis type 2
autosomal dominant
