Endocrine genetics

Question 1

monogenic

Answer 1

refers to traits controlled by a single gene

a mutation or variation in that one gene directly affects the trait

Question 2

polygenic inheritance

Answer 2

refers to traits influenced by multiple genes often located on different chromosomes which each contributing a small effect to the phenotype

Question 3

what are monogenic disease often assoc with

Answer 3

either single nucleotide variants or small insertions or deletions

Question 4

what do small inseertions and deltions result in

Answer 4

In-frame indels: result in gains or losses of amino acids, amino acid substitutions or generation of premature stop codons or defects in splicing

Out-of frame indels: typically result in frameshift changes that frequently result in premature truncation of the encoded protein

Loss of Function (LOF) mutations typically result from nonsense, frameshift or canonical splice site mutations

Question 5

what do single nucleotide variants reuslt in

Answer 5

Missense amino acid change (i.e. substitution of one amino acid with another)

Nonsense amino acid change (i.e. generation of a stop codon)

Splice site alteration (e.g. defective splicing from change to donor or acceptor splice site)

Question 6

pre genetic tets

Answer 6

ENDOCRINOLOGIST

Clinical assessment
Indication for testing
Request (Consent)

Question 7

genetic testing

Answer 7

GENETICS TEAM

Single gene test
Gene Panels
(CGH array, WGS)

Question 8

post genetic test

Answer 8

ENDOCRINOLOGIST

Understand report
Clinical-Genetic Diagnosis
?Further Action

Question 9

example of monogenic endocrine disease

Answer 9

• MEN type 1 and 2
• Von Hippel-Lindau
• Neurofibromatosis type 1
• Carney complex
• McCune-Albright Syndrome
• Phaechromocytoma/paraganglioma

Question 10

Key featires of MEN1

Answer 10

parathyroid tumours
pituitary adenomas

Question 11

multiple endocrine neoplasia 1

Answer 11

rare hereditary disorder characterized by the development of tumors in multiple endocrine glands.

Question 12

what does menin play a role in

Answer 12

tumour suppression so mutations can lead to unregulated cell growth

Question 13

what is MEN1 caused by

Answer 13

gene mutation in MEN1 which encodes a protein called menin

Question 14

inheritance of MEN1

Answer 14

autosomal dominant

Question 15

MEN2

Answer 15

predisposes individuals to develop tumors in endocrine glands
men2a more common

Question 16

What is met2 caused by

Answer 16

mutations in the RET proto-oncogene, which is involved in cell growth and development

Question 17

von hippel lindau syndromw

Answer 17

Inherited disorder causing multiple tumours, both benign and malignant, in the central nervous system (CNS) and viscera

Question 18

what inheritance mode is von hippel

Answer 18

autosomal dominantn

Question 19

neurofibromatosis type 1

Answer 19

genetic condition causing tumours along nervous system
relatively common
mutation in NF1 gene

Question 20

presentation of neurofibromatosis type 1

Answer 20

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

Phaeochromocytoma (rare)

Question 21

carney complex

Answer 21

Rare genetic disorder characterized by multiple benign tumours (multiple neoplasia) most often affecting the heart, skin and endocrine system and abnormalities in skin pigmentation