Lecture 42

Question 1

Mutation of which gene result in Immunodeficiency-centromeric instability-facial anomalies syndrome (ICF syndrome)

Answer 1

Dnmt3b, which result in hypomethylation on Chr 1,9,16

- centromere instability of these chromosomes is critical for B cell development

Question 2

X- linked dominant

• seizures, loss of speech and acquired hand skills
• irregular breathing and motor control problems

Answer 2

Rett syndrome

Question 3

Mutation of which gene result in Rett syndrome

Answer 3

Mutation in X-linked gene- MeCP2, leading to genes not repressed in brain

Question 4

Genetic cause of Beckwith-Wiedemann Sydrome (BWS) (3)

Answer 4

1. maternal chromosomal rearrangements of 11p15 (imprinted region)
2. Paternal uniparental disomy
3. Abnormal methylation at 11p15

Question 5

Macroglossia, 
somatic overgrowth, 
birthweight and length greater than 90 percentile
unbilical hernia
ear crease
neonatal hypoglycemia

Answer 5

Beckwith-Wiedemann Sydrome (BWS)

* Children born of IVF has higher chance of BWS, because IVF causes abnormal DNA methylation of region 11p15.

Question 6

Relationship between CDKN2B and decitabine

Answer 6

CDKN2B is tumour suppressor gene, also called p15.
Decitabine is DNA hypomethylating agent.
In normal cell, CDKN is unmethylated, which prevents malignant transformation, inhibiting cyclin dependent kinases
But in cancer call, CDKN is methylated, thus leading to uncontrolled cell division.
But decitabine can be used to reduce methylation.

Question 7

How does DNA hypomethylation agents work?

Answer 7

It is cytidine analogue, which is incorporated in DNA/RNA. It has nitrogen at position5, so methyl group can’t be added, thus preventing methylation. Also it is known that these agent bind and inhibit DNA methyltransferase enzyme`

Question 8

Environmental factors that influence epigenetics

Answer 8

Temperature
Toxin
Maternal care (maternal nutrition)
- increased post-natal care, reduced methylation of promoter of glucocorticoid receptor, so can handle stress better
Diet
Hypoxia
*Different environment causes epigenetic drift
eg) old twins have different epigenetic marker than young twins

Question 9

Incontinentia pigmenti inheritance

Answer 9

X-linked dominant (IKBKG gene)