Genetics Flashcards
What is meant by a monogenic gene disorder?
Due to a single gene mutation
What are the 6 patterns of inheritance by which a monogenic gene disorder can be passed on?
Autosomal Dominant Autosomal Recessive X linked dominant X linked recessive Y-linked Mitochondrial
What is meant by a polygenic gene disorder?
- Multiple genes involved
- Often environmental influences
- Evaluated by looking at large populations
Describe what is meant by high penetrance?
If the patient has the gene mutation they are extremely likely to have the disease
If both parents are carriers for a recessive mutation, what is the likelihood of the child inheriting the disease?
1 in 4
Autosomal dominant usually skips generations. TRUE/FALSE?
FALSE
usually appears in every generation
If males can only pass a genetic disorder to females, but females can pass it to either sex, what pattern of inheritance is this?
X-linked dominant
If males are always affected, yet females can become carriers, what pattern of inheritance does this describe?
X-Linked Recessive
If only males are affected by a genetic disease, what does this indicate about its inheritance pattern?
It is Y-linked as only males have a Y-chromosome
Describe what is meant by a mitochondrial inheritance pattern
Inherited through mother’s mitochondrial DNA whilst in the womb
=> can only inherit it from mother
Explain what benign tumours usually present in Multiple Endocrine Neoplasia Type 1 (MEN1)
Benign:
- Non-secreting Islet cell tumour
- Non-secreting pituitary tumour
- adrenal cortex
What malignant tumour usually presents in MEN1?
Foregut carcinoid tumour
secretes gastrin, glucagon and polypeptides
What benign or malignant tumours are found in Multiple Endocrine Neoplasia Type 2?
C-cell
Adrenal Chromaffin
What gene defect is found in Multiple Endocrine Neoplasia Type 2?
RET
What hormones are secreted in Von Hippel Lindau syndrome?
Catecholamines
What type of gene is the MEN1 gene
A tumour suppressor
What section of the MEN1 gene is usually mutated in Multiple endocrine Neoplasia Type 1?
11q
Both MEN1 and MEN2 are autosomal dominant. TRUE/FALSE?
TRUE
What section of the RET gene is usually mutated in MEN2 and what type of gene is it?
10q
RET = proto-oncogene
MEN mutations in MEN1 usually occur in very specific areas of the codon. TRUE/FALSE?
FALSE
RET mutations in MEN2 act in very specific cysteine residues, whereas in MEN1 they can occur anywhere along the length of the codon.
What three areas are usually affected by tumours in MEN1?
Pituitary
Pancreas
Parathyroid
What tumour found during MEN1 is the most fatal?
Pancreatic neuroendocrine tumour
After what size should an MEN1 pancreatic tumour be referred for surgical intervention?
> 2cm
What tumours usually present in MEN2a?
Parathyroid hyperplasia
Medullary Thyroid Carcinoma
Phaechromocytoma
What tumours are usually present in MEN2b?
Mucosal Neuromas
Medullary Thyroid Carcinoma
Phaechromocytoma
Marfan’s Syndrome is also present
What prophylactic treatment can be used in MEN2 for Medullary Thyroid Cancer?
Prophylactic Thyroidectomy
At what age is it important to screen for Phaechromocytoma and Parathyroid disease?
Between ages 11 and 16
>11 = High Risk
>16 = moderate Risk
How do patients with Carney Complex usually present?
Spotty pigmentation of the skin:
- lips
- eyes
- genitals
Where do myxomas usually present in Carney Complex patients?
Breast
Cardiac
generally myxomas can be cutaneous or mucosal
What cancers often present in the Carney Complex
Thyroid carcinoma
GH producing pituitary Adenoma (causing Acromegaly)
What feature of the Carney Complex leads to the development of Cushing’s syndrome?
Primary pigmented nodular adrenocortical disease
PPNAD causes adrenal glands to produce excess cortisol
=> Cushing’s syndrome
What subunit involved GPCR signalling caused uncontrolled proliferation in the Carney complex?
Protein Kinase A (PKA) regulatory subunit
WHat are the usual presenting features of McCune-Albright syndrome?
- Café-au-lait skin pigmentation (looks like Maine coast)
- Polyostotic fibrous dysplasia (bones)
- Precocious puberty (typically females)
- Thyroid nodules
- GH excess
- Cushing’s syndrome (adrenal)
When does the mutation in McCune-Albright syndrome occur?
Post-zygotic somatic mutation
=> not inherited from mother
What gene is affected in Von Hippel Lindau syndrome and what inhertance pattern does it exhibit?
VHL gene
Autosomal Dominant
What type of tumour is most common in VHL?
Vascular tumours
e.g. Retinal Haemangiomas
CNS Haemangioblastomas
What signs are often seen in Neurofibromatosis Type 1?
Axillary freckling Café-au-lait patches Neurofibromas Optic gliomas Scoliosis Some learning difficulties
What rare type of cancer can present in Neurofibromatosis Type 1?
Phaeochromocytoma (rare)
What is a phaechromocytoma usually referred to as?
The tumour of 10 e.g. 10% malignant 10% bilateral 10% extra-adrenal 10% familial etc.
What gene mutations commonly cause Paragangliomas?
SDHA, SDHB, SDHC, SDHD
Succinate Dehydrogenase A,B,C,D
What Succinate Dehydrogenase mutation is worst to have and why?
SDHB
most likely to cause malignancy (B for Bad)
What succinate Dehydrogenase mutation can be inherited from a father?
SDHD
D for Dad
