Imprinting

Question 1

Mechanisms by which Beckwith Wiedemann syndrome occurs

Answer 1

• loss of methylation of IC2 on maternal chromosome (40-50%) (results in CDKN1C not being expressed)
• gain of methylation of IC1 on mat chrom (5-8%)
• mosaic paternal UPD (20%)
• CDKN1C mutation on mat chrom (40%)
• Dups or dels of 11p15.5 eg dup pat 11p15 leads to over exp of IGF2.

Question 2

Mechanisms of silver Russel syndrome

Answer 2

1. loss of methylation of paternal IC1 which leads to biallelic silencing of IGF2.
2. Segmental dup of mat 11p15.5. How this causes SRS is unclear.
3. UPD mat chrom 7. (7p11-p13 and 7q31)

Question 3

six imprinted regions

Answer 3

6q24
chr7
11p15.5
14q32
15q11.2
20q13.2

Question 4

mechanisms leading to imprinting disorders

Answer 4

1. UPD
2. deletion of a gene
3. duplication of a gene
4. epigenetic mutation resulting in loss of correct methylation
5. mutation on active allele

Question 5

familial biparental hydatiform mole

Answer 5

only known pure maternal effect recessively inherited disorder in humans.
phenotypically normal female suffers repeated pregnancy loss due to development of complete mole
results from genome wide failure to define or maintain maternal epigenotype at imprinted loci.
two possible gebes NLRP7 and KHDC3L.