Genetics

Question 1

What is meant by a monogenic gene disorder?

Answer 1

Due to a single gene mutation

Question 2

What are the 6 patterns of inheritance by which a monogenic gene disorder can be passed on?

Answer 2

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

Question 3

What is meant by a polygenic gene disorder?

Answer 3

• Multiple genes involved
• Often environmental influences
• Evaluated by looking at large populations

Question 4

Describe what is meant by high penetrance?

Answer 4

If the patient has the gene mutation they are extremely likely to have the disease

Question 5

If both parents are carriers for a recessive mutation, what is the likelihood of the child inheriting the disease?

Answer 5

1 in 4

Question 6

Autosomal dominant usually skips generations. TRUE/FALSE?

Answer 6

FALSE

usually appears in every generation

Question 7

If males can only pass a genetic disorder to females, but females can pass it to either sex, what pattern of inheritance is this?

Answer 7

X-linked dominant

Question 8

If males are always affected, yet females can become carriers, what pattern of inheritance does this describe?

Answer 8

X-Linked Recessive

Question 9

If only males are affected by a genetic disease, what does this indicate about its inheritance pattern?

Answer 9

It is Y-linked as only males have a Y-chromosome

Question 10

Describe what is meant by a mitochondrial inheritance pattern

Answer 10

Inherited through mother’s mitochondrial DNA whilst in the womb
=> can only inherit it from mother

Question 11

Explain what benign tumours usually present in Multiple Endocrine Neoplasia Type 1 (MEN1)

Answer 11

Benign:

• Non-secreting Islet cell tumour
• Non-secreting pituitary tumour
• adrenal cortex

Question 12

What malignant tumour usually presents in MEN1?

Answer 12

Foregut carcinoid tumour

secretes gastrin, glucagon and polypeptides

Question 13

What benign or malignant tumours are found in Multiple Endocrine Neoplasia Type 2?

Answer 13

C-cell

Adrenal Chromaffin

Question 14

What gene defect is found in Multiple Endocrine Neoplasia Type 2?

Answer 14

RET

Question 15

What hormones are secreted in Von Hippel Lindau syndrome?

Answer 15

Catecholamines

Question 16

What type of gene is the MEN1 gene

Answer 16

A tumour suppressor

Question 17

What section of the MEN1 gene is usually mutated in Multiple endocrine Neoplasia Type 1?

Answer 17

11q

Question 18

Both MEN1 and MEN2 are autosomal dominant. TRUE/FALSE?

Answer 18

TRUE

Question 19

What section of the RET gene is usually mutated in MEN2 and what type of gene is it?

Answer 19

10q

RET = proto-oncogene

Question 20

MEN mutations in MEN1 usually occur in very specific areas of the codon. TRUE/FALSE?

Answer 20

FALSE
RET mutations in MEN2 act in very specific cysteine residues, whereas in MEN1 they can occur anywhere along the length of the codon.

Question 21

What three areas are usually affected by tumours in MEN1?

Answer 21

Pituitary
Pancreas
Parathyroid

Question 22

What tumour found during MEN1 is the most fatal?

Answer 22

Pancreatic neuroendocrine tumour

Question 23

After what size should an MEN1 pancreatic tumour be referred for surgical intervention?

Answer 23

> 2cm

Question 24

What tumours usually present in MEN2a?

Answer 24

Parathyroid hyperplasia
Medullary Thyroid Carcinoma
Phaechromocytoma

Question 25

What tumours are usually present in MEN2b?

Answer 25

Mucosal Neuromas Medullary Thyroid Carcinoma Phaechromocytoma **Marfan's Syndrome is also present**

Question 26

What prophylactic treatment can be used in MEN2 for Medullary Thyroid Cancer?

Answer 26

Prophylactic Thyroidectomy

Question 27

At what age is it important to screen for Phaechromocytoma and Parathyroid disease?

Answer 27

Between ages 11 and 16 >11 = High Risk >16 = moderate Risk

Question 28

How do patients with Carney Complex usually present?

Answer 28

Spotty pigmentation of the skin: - lips - eyes - genitals

Question 29

Where do myxomas usually present in Carney Complex patients?

Answer 29

Breast Cardiac *generally myxomas can be cutaneous or mucosal*

Question 30

What cancers often present in the Carney Complex

Answer 30

Thyroid carcinoma | GH producing pituitary Adenoma (causing Acromegaly)

Question 31

What feature of the Carney Complex leads to the development of Cushing's syndrome?

Answer 31

Primary pigmented nodular adrenocortical disease PPNAD causes adrenal glands to produce excess cortisol => Cushing's syndrome

Question 32

What subunit involved GPCR signalling caused uncontrolled proliferation in the Carney complex?

Answer 32

Protein Kinase A (PKA) regulatory subunit

Question 33

WHat are the usual presenting features of McCune-Albright syndrome?

Answer 33

- 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)

Question 34

When does the mutation in McCune-Albright syndrome occur?

Answer 34

Post-zygotic somatic mutation | => not inherited from mother

Question 35

What gene is affected in Von Hippel Lindau syndrome and what inhertance pattern does it exhibit?

Answer 35

VHL gene | Autosomal Dominant

Question 36

What type of tumour is most common in VHL?

Answer 36

Vascular tumours e.g. Retinal Haemangiomas CNS Haemangioblastomas

Question 37

What signs are often seen in Neurofibromatosis Type 1?

Answer 37

``` Axillary freckling Café-au-lait patches Neurofibromas Optic gliomas Scoliosis Some learning difficulties ```

Question 38

What rare type of cancer can present in Neurofibromatosis Type 1?

Answer 38

Phaeochromocytoma (rare)

Question 39

What is a phaechromocytoma usually referred to as?

Answer 39

``` The tumour of 10 e.g. 10% malignant 10% bilateral 10% extra-adrenal 10% familial etc. ```

Question 40

What gene mutations commonly cause Paragangliomas?

Answer 40

SDHA, SDHB, SDHC, SDHD | Succinate Dehydrogenase A,B,C,D

Question 41

What Succinate Dehydrogenase mutation is worst to have and why?

Answer 41

SDHB | most likely to cause malignancy (B for Bad)

Question 42

What succinate Dehydrogenase mutation can be inherited from a father?

Answer 42

SDHD | D for Dad