Fragile X syndrome: diagnosis by molecular characterization of  gene and clinical correlation

Abd El-Ghany, Hoda M.; Ehssan, Eman A.; El-Deen, Menatalla K.; Al-Gamal, Rasha A.; Samy, Rania M.; El-Deen, Amany S.

doi:10.4103/MXE.MXE_11_18

Fragile X syndrome: diagnosis by molecular characterization of gene and clinical correlation

Authors

Abstract

Background
One of the most common forms of inherited intellectual disability (ID) is fragile X syndrome (FXS), which is caused by expansion of cytosine–guanine–guanine trinucleotide repeat at the 5′ untranslated region of the fragile X mental retardation gene () at Xq27. The cytosine–guanine–guanine repeat expansion leads to hypermethylation and inactive transcription of the gene. The present study aimed to detect expected gene alleles by methylation-sensitive PCR and its clinical correlation for rapid screening of FXS among male patients with ID.
Patients and methods
The study included 50 male patients with ID and clinical features suggestive of FXS, who were compared with 50 healthy age-matched volunteers. All patients were subjected to full history taking, thorough clinical examination using a 15-item checklist [physical (big ears, joint hyperextensibility, Simian crease, wide forehead, macroorchidism, and elongated face) and neurological features (mental retardation, family history of mental retardation, poor eye contact, hand biting, hyperactivity, perservative speech, tactile defensiveness, hand flapping, and short attention span)], and karyotyping using GTG banding. Methylation-sensitive PCR technique after bisulfite treatment of DNA was applied for the detection of expanded alleles of the gene.
Results
Clinical score in patients with abnormal alleles was significantly higher compared with patients with normal alleles. GTG-banding technique showed normal 46XY male karyotype for studied patients. Frequency of normal gene alleles was detected in the control group (100%) and 44 (88%) patients. Abnormal alleles were detected in six (12%) patients: three (6%) patients with full mutation (FM) and three (6%) patients with premutation carrier.
Conclusion
Our study revealed that PCR-positive results of fragile X correlate with the checklist clinical score rather than a single clinical entity.

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