Exp Mol Med.  2003 Apr;35(2):113-117.

De novo mutations in sporadic deletional Duchenne muscular dystrophy (DMD) cases

• Mukherjee
• Chaturvedi LS
• Srivastava S
• Mittal RD
• Mittal B

Abstract

Dinucleotide repeat polymorphism based genetic analysis is a powerful approach to gain insight into rare genetic events like germline mosaicism and de novo mutations. The loss of heterozygosity of polymorphic dinucleotide loci at "deletional hotspot" of dystrophin gene can provide direct evidence of carrier status in female relatives of affected DMD patients with overlapped exonic deletions. We have used 4 STR loci of the central deletional hotspot of the dystrophin gene for genetic analysis in sporadic unrelated DMD families. Twenty-nine mothers of sporadic deletional cases were analysed and their carrier status was determined. Eighteen of them showed heterozygosity in the deleted loci suggesting the occurrence of de novo mutations. In 9 cases, the carrier status was indeterminate while 2 showed germline mosaicism. Our observations reiterated the importance of STR analysis in determining the status of mothers of sporadic deletional DMD cases in order to provide proper genetic counselling.

Keyword

dinucleotide repeats; germline mutation; heterozygote detection; mosaicism; muscular dystro-phy; Duchenne; polymorphism

MeSH Terms

DNA Mutational Analysis
Dystrophin/*genetics
Female
Germ-Line Mutation/genetics
Haplotypes/genetics
Heterozygote Detection
Human
Male
Mosaicism/genetics
Muscular Dystrophy, Duchenne/*genetics
Mutation/*genetics
Pedigree
Sequence Deletion/genetics