| BRIEF REPORT |
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| Year : 2010 | Volume
: 1
| Issue : 1 | Page : 26-30 |
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A PCR-based screening method for rapid detection and genetic counseling in Fragile-X syndrome
Usha Dave1, Dhanlaxmi Shetty2
1 Principal Scientist-R &D, Super Religare Labs, Mumbai, India
2 Post-Doc. Research Fellow, Super Religare Labs, Mumbai, India
Correspondence Address:
Usha Dave
Super Religare Labs. (SRL), Plot No. 1, Prime Building, S. V. Road, Goregaon (W), Mumbai-400 062
India
DOI: 10.4103/0976-1756.62140
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The Fragile-X syndrome (FXS), an X-linked disorder, is recognized as the second common cause of mental retardation after Down syndrome. It is associated with a variety of neurobehavioral deficits, including cognitive dysfunction, attention-deficit /hyperactivity, autism spectrum disorders, and other emotional problems. FXS is caused by full mutation (> 200 CGG repeats) in FMR1 (fragile X mental retardation 1 gene). This dynamic mutation of FMR1 is due to progressive expansion of polymorphic (CGG)n trinucleotide repeats located in the promoter region of the FMR1 at Xq27.3 causing decreased or absent levels of fragile X mental retardation protein (FMRP). The smaller expansion (55-200 CGG) of FMR1 is termed a premutation, often found in mothers of FXS and also in premutation carriers with varying degrees of physical phenotypes and intellectual impairment correlated with the magnitude of FMRP deficit. Both full mutation and premutation makes FXS a family concern as an array of disabilities are seen throughout multiple generations. The aim of the study was thus to establish the polymerase chain reaction (PCR)-based method as a routine screening method for rapid detection of FXS. In view of this, total 720 MR children were selected for cytogenetic and further molecular investigation to check the reliability of the PCR method. The chromosomal analysis conducted in 443 children revealed 20 (4.5%) subjects with fragile site on X-chromosome, characteristic of FXS. Molecular study conducted on 12/65 cases showed (18.46%) to be positive by PCR technique and was confirmed by Southern Blotting. The clinical and dysmorphic features though well-described, are often mild and subtle; as a result go unnoticed by the clinicians. It is therefore important for a clinician who is not so equipped with genetic knowledge in India, to address the issues of transmission and genetic counseling to family members emphasizing the genetic testing in mental retardation (MR), associated learning and behavioral problems. This relatively simple and accurate molecular test was used to screen all patients with unexplained mental retardation/ learning impairment for FXS. The detection of FMR1 mutation was found helpful in informed genetic counseling for medical management, prenatal diagnosis and follow-up. |
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