Fragile X syndrome

acorrigan's version from 2017-05-09 20:59


Question Answer
What is the cause of FraX?CCG trinucleotide repeat expansion in the 5'-UTR of the FMR1 gene
What is the mode of inheritance?X-linked dominant
What are the minimal commissioning criteria for fraX testing?Minimum age 5 years, moderate to severe developmental developmental delay
What array result would stop fraX testing going ahead?Class 4 or 5, pathogenic likely or abnormal
What are the common physical characteristics of fragile X?Dysmorphic facial features including elongated jaw, prominent ears & jaw, large head circumference; macroorchidism becomes apparent at puberty
What happens to expanded repeats and how does this affect the gene?The expanded repeats are methylated and this leads to silencing of the gene.
Why is accurate repeat sizing important?Affects penetrance & risk to subsequent generations of the family
How is FraX tested?QF-PCR and capillary electrophoresis for sizing
How accurate is the standard test?Accurate up to ~58
What kit is used for pre-mutation and full mutation carriers and why?Amplidex, it's more accurate at sizing larger repeats
How many repeats show full penetrance?>200
How many repeats are in a premutation?59-200
What symptoms might premutations cause? Carrier females - premature ovarian insufficiency. Males - fragile X associated tremor ataxia syndrome
What may happen to carrier females with 55-200 repeatsAt these numbers the repeat becomes unstable and may expand during transmission to the next generation; therefore these women are at risk of having affected offspring
Does expansion to full mutation happen in both males and females?No only in females
What issues can be encountered when analysing fragile X results?Stutter peaks, preferential amplification of the smaller allele which can lead to failure of automatic labelling of these peaks