Fragile X/POF

Question 1

Where do referrals for fragile X testing due to POF usually come from?

Answer 1

Gynaecology dept investigating infertility

Question 2

Definition of POF?

Answer 2

Loss of ovarian function prior to age 40

Question 3

Classical features of Fragile X?

Answer 3

Characteristic facial features- large ears, long face
Hyperextensible fingers and thumbs
Learning difficulties
Macro-orchidism

Question 4

Causative mutation of Fragile X?

Answer 4

X-linked dominant triplet repeat expansion (CGG) in the 5’ UTR of FMR1 gene within exon 1

Question 5

Genotype-phenotype correlation in Fragile X?

a) >200
b) 59-199
c) 46-58
d) >45

Answer 5

a) full mutation, causes FMR1 metylation (all males have learning difficulties as well as 50% females)
b) women are pre-mutation carriers, males are normal transmitting males
c) intermediate group- chance of expansion in future generations but risk to their own children is small
d) normal

Question 6

What are the risks of being a pre-mutation carrier? (3)

Answer 6

Expansion to full mutation in their children
POF
FX-associated ataxia