Fragile X syndrome – detection of CGG repeat expansion in the FMR1 gene

Clinical expertise code:

208

Test without reimbursement:

YES

Gender:

Woman

Material:

Peripheral blood, Isolated DNA from blood

Turnover time:

3 weeks

STATIM:

3 days

Material:

Peripheral blood | 1x 3 ml of whole blood in K3 EDTA tube

Storage after examination: week after the report is issued 2 – 8°C

Isolated DNA from blood | 10–100 ng/μL of isolated DNA from blood in a PCR tube of at least 15 μL.

Storage after examination: stored in a DNA archive without restriction 15°C

Quick test description:

The testing is performed to determine the presence and extent of CGG triplet expansion in the IT15 region of the FMR1 gene.

Test details:

Fragile X chromosome syndrome (FRAXA, Martin-Bell syndrome) is the second most common cause of mental retardation in men after Down syndrome. This syndrome is an X-linked hereditary disease manifested by mental retardation often associated with dysmorphic features. Phenotypic manifestation in prepubertal men is relatively non-specific and variable, which makes clinical diagnosis difficult.

Women may also be affected. Approximately half of carriers of the full mutation have mild to moderate forms of mental retardation. The syndrome occurs with a frequency of approximately 1:3,000–4000 in males and 1:8,000 in females and is caused in most cases by a dynamic mutation – expansion of CGG trinucleotides above 200 replicates in the 5'-untranslated part of the FMR1gene localised in the Xq27.3 region. Subsequent hypermethylation of the promoter region causes the silencing of FMR1 gene expression. Due to mitotic mutation instability, some patients exhibit somatic mosaicism (co-existence of premutation and full mutation), which explains the large variability of clinical manifestation. The screening of FRAXA syndrome is performed in a cascade.

Using the FRAXA screen method, we first detect healthy to premutated alleles up to 120 CGG repeats. If we prove an expanded allele or obtain an informative result, we continue with another FRAXA expand analysis, which in the case of examination in a woman determines the homozygous form of the allele and in both sexes determines the number of repeats and specifies the type of expanded allele (intermediate, premutation or full mutation).

Reference values:
normal allele: 6–44 repeats;
intermediate allele: 45–54 repeats;
allele with premutation: 55–200 repeats;
allele with full mutation: more than 200 repeats

Indication

patient with mental retardation or delayed mental development and/or phenotypic features for FRAXA, relatives of the patient with FRAXA and detected FMR1 gene mutation, relatives of female carriers of a premutation or intermediate allele in the FMR1 gene, prenatal diagnosis in female carriers of a premutation or mutation in the FMR1 gene, women with POF, preconception testing in women whose parent has a tremor

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