Molecular analysis of fragile X syndrome (FXS) among Malaysian patients with developmental disability
- Author:
Ernie Zuraida Ali
;
Yusnita Yakob
;
Norsiah Md Desa
;
Taufik Ishak
;
Zubaidah Zakaria
;
Lock-Hock Ngu
;
Wee-Teik Keng
- Publication Type:Original Article
- Keywords:
fragile X syndrome;
FXS;
CGG repeat;
FMR1 gene;
prevalence
- From:The Malaysian Journal of Pathology
2017;39(2):99-106
- CountryMalaysia
- Language:English
-
Abstract:
Fragile X syndrome (FXS) is a neurodevelopmental disorder commonly found worldwide, caused
by the silencing of fragile X mental retardation 1 (FMR1) gene on the X-chromosome. Most of the
patients lost FMR1 function due to an expansion of cytosine-guanine-guanine (CGG) repeat at the
5’ untranslated region (5’UTR) of the gene. The purpose of this study is to identify the prevalence of
FXS and characterize the FMR1 gene CGG repeats distribution among children with developmental
disability in Malaysia. Genomic DNA of 2201 samples from different ethnicities (Malays, Chinese,
Indian and others) of both genders were PCR-amplified from peripheral blood leukocytes based on
specific primers at 5’UTR of FMR1 gene. Full mutations and mosaics were successfully identified
by triple methylation specific PCR (ms-PCR) and subsequently verified with FragilEase kit. The
findings revealed for the first time the prevalence of FXS full mutation in children with developmental
disability in Malaysia was 3.5%, a slightly higher figure as compared to other countries. Molecular
investigation also identified 0.2% and 0.4% probands have permutation and intermediate alleles,
respectively. The CGG repeats length observation showed 95% of patients had normal alleles within
11 to 44 CGG repeats; with 29 repeats found most common among Malays and Indians while 28
repeats were most common among Chinese. In conclusion, this is the first report of prevalence and
characterisation of CGG repeats that reflects genetic variability among Malaysian ethnic grouping.
