Fragile X Syndrome (FXS)

There may be a more appropriate test, please see: Fragile X (associated) Primary Ovarian Insufficiency (FXPOI); Premature Ovarian Failure 1 (POF1), Fragile X (associated) Tremor/Ataxia Syndrome (FXTAS)

Introduction

Fragile X syndrome is an X-linked disorder, characterized by moderate to severe mental retardation, macroorchidism, and distinct facial features, including long face, large ears, and prominent jaw, in males; with a milder phenotype in females.  In >99% of cases, the disorder is caused by the unstable expansion of a CGG repeat (to more than ~200 repeats)  in the FMR1 gene at Xq27.3 and abnormal methylation, which results in suppression of FMR1 transcription and decreased protein levels in the brain.

Referral information

We accept referrals for confirmation of clinical diagnosis in patients meeting criteria issued by UKGTN referred with a fully completed UKGTN FMR1 form. Testing is also available for patients with a FMR1 associated disorder (FXTAS/FXPOI) and for families with a history of Fragile X syndrome.

Technical information

Size analysis of the (CGG)n repeat region of the FMR1 gene is undertaken using PCR based technologies (Standard FMR1 PCR and/or AmplideX™ FMR1 PCR and, if requested,  AmplideX™ FMR1 methylation PCR) – see test validation details below.

Price & reporting times

NHS referrals to this service are paid for where there is an existing specialist commissioning contract for genetic testing. In other cases please contact the lab for prices.

Test Price (NHS) Price (non-NHS) TRT (Calendar days)
Standard FMR1 PCR test/ AmplideX™ FMR1 PCR test POA POA 28
AmplideX™ FMR1 methylation PCR test POA POA 28
Urgent testing (e.g pregnant parent) POA POA 14
Prenatal diagnosis POA POA 3

Test validation & quality assurance - information for users

The Standard FMR1 PCR test is used to detect the size of “Normal” and “Intermediate” and some of the smaller “Premutation” alleles of the FMR1 CGG triplet repeat region. Larger “Premutation” and “Full Mutation” expansions cannot be detected with this method, and it is therefore used only as an “exclusion” test. If the Standard FMR1 PCR test results are inconclusive, the AmplideX™ FMR1 PCR test is performed (using a commercial kit, www.asuragen.com). This enables the detection of FMR1 repeat alleles up to and including full mutations (>200 repeats). Sizing accuracy for both tests is estimated to be +/-2 repeats for alleles in the Normal, Intermediate and Premutation ranges. The FMR1 PCR analysis has a sensitivity and specificity of >98%. The testing is therefore effective for exclusion of Fragile X syndrome as a likely diagnosis and for detection of FMR1 carrier status. If requested, the methylation status of expanded alleles may be determined using a separate commercial kit, AmplideX™ FMR1 methylation PCR test.

Referral guidelines

Please see our referral guidelines for more information.

OMIM Number(s) - 300624

Gene(s) - FMR1

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