Deletional mutations of dystrophin gene and carrier detection in eastern India.

ABSTRACT

Objective. To determine the pattern of deletions of the dystrophin gene, the major class of mutations among the Duchenne and Becker muscular dystrophy patients of eastern India and to analyze the carrier frequency of the female members of the proband’s family. Methods. Deletional mutations occurring in patients have been characterized by multiplex polymerase chain reaction. Carrier state of mothers and sisters of probands were analyzed by either of two methods: 1) typing polymorphic short tandem repeat markers in or around the regions of deletion, by radioactive polymerase chain reaction and 2) quantitative real time amplification of the region of deletion. Results. Deletions were detected in 67 (62.04%) out of 108 male patients, about 76.12% of these being localized in the central hot spot region of the gene, i.e., between exon 42 to exon 53 and 17.91% at the proximal hot spot i.e., between exon 1 to exon 20. In the present study were found 43 types of deletions, out of which 25 (58%) were new deletions, which were not described earlier among the Indian patients. Distribution pattern of deletions in different hot spot regions has been compared with that of other countries and statistical analysis reveals significant difference between countries (p<0.001). Correlation of the pattern of deletion with clinical phenotype of patients has been discussed. Interesting case of germline mosaicism and its implications in counseling has also been discussed. Conclusion. About half the mothers of affected probands were not carriers of the deletion, underscoring the need to use real time techniques for carrier detection.