Genetics

Question 1

What is a monogenic disorder

Answer 1

Disorders that arise from a defect in a single gene

tend to be rarer and higher penetrance

Question 2

What is a polygenic disorder

Answer 2

Disorder caused by multiple genes
Often has environmental influences
Tend to be low penetrance

Question 3

List the 6 patterns of monogenic inheritance

Answer 3

Autosomal dominant 
Autosomal recessive 
X-linked dominant 
X-linked recessive 
Y-linked 
Mitochondrial

Question 4

What is meant by low penetrance when discussing disease

Answer 4

low risk of disease presentation even if you have the genetic variant

Question 5

What are some of the main indicators of genetic disease

Answer 5

Childhood/early onset,
Familial history
Features consistent with specific genetic disorder

Question 6

Which type of genetic pattern is the most valuable for testing

Answer 6

High disease severity with high penetrance is the most valuable for genetic testing

Question 7

Describe the genetic cause of MEN1

Answer 7

Autosomal dominant pattern
Caused by defect in the MEN1 gene which is a tumour suppressor
Mutations result in loss/reduced protein function and occur throughout the coding region

Question 8

What are the symptoms of MEN1

Answer 8

Characterised by the development of neuroendocrine tumours

3 P’s tumour (pituitary, parathyroid and pancreas )

Question 9

What are the symptoms of MEN2

Answer 9

Will develop medullary thyroid cancer, parathyroid and adrenal tumours

Question 10

Describe the genetic cause of MEN2

Answer 10

Autosomal dominant pattern
Mutation in the RET gene
Proto-oncogene
RET mutations affect specific cysteine residues
Mutations result in activation of receptor tyrosine kinase

Question 11

What is PPNAD

Answer 11

Primary pigmented nodular adrenocortical disease

Causes adrenal glands to produce excess cortisol leading to the development of Cushing’s syndrome

Question 12

What does mutation in the VHL gene cause

Answer 12

Von Hippel-Lindau disease
Autosomal dominant pattern
Tumour suppressor gene so results in many different types of tumour forming
Leads to excess of catecholamine

Question 13

Describe the genetics of the Carney Complex

Answer 13

Mutation in PRKAR1A
Defective regulatory subunit
Aberrant PKA signalling
Uncontrolled proliferation

Question 14

What are the symptoms of the Carney complex

Answer 14

Spotty skin pigmentation 
Myxoma 
PPNAD 
Acromegaly 
Thyroid carcinoma 
etc.....

Question 15

What are the symptoms of McCune Albright Syndrome

Answer 15

Café au lait spots - often on one side/area 
Polyostotic fibrous dysplasia - bones 
Precocious puberty 
Pituitary GH excess 
Thyroid nodules 
Cushing's

Question 16

Describe the genetics of McCune Albright Syndrome

Answer 16

Due to post-zygotic somatic mutation – occurs early in development but isn’t inherited from parents
Associated with defects in G protein signalling pathway – mutation in alpha subunit

Question 17

What are the symptoms of neurofibromatosis type 1

Answer 17

Axillary freckling
 Café-au-lait patches
 Neurofibromas
 Optic gliomas
 Scoliosis
 Learning difficulties in some
Phaeochromocytoma (rare)

Question 18

What gene causes neurofibromatosis type 1

Answer 18

Mutation in NF1 gene

Very common condition