Detection of pathogenic mutations and the mechanism of a rare chromosomal rearrangement in a Chinese family with Becker muscular dystrophy

Abstract

Objective: The objectives of this research are to genetically diagnose a family with Becker muscular dystrophy (BMD), to explore the molecular mechanism of the disease, and to predict the possibility of BMD development in two individuals who have not yet reached the age of onset (young individuals).

Methods: The multiplex polymerase chain reaction was first employed to screen dystrophin (DMD) gene deletions, and the locations of deletion breakpoints were identified using the Sequenom platform and long-range PCR. Sanger sequencing was then performed for the undeleted exons.

Results: All BMD patients and a young individual carry a deletion spanning exons 45 to 53 and an unreported missense mutation on exon 11 of the DMD gene. This point mutation was screened in 412 healthy individuals and heterozygous genotype was found in two females. Determination of deletion breakpoints demonstrated a 330-kb deletion and there was a 9-bp insertion between the breakpoints. This 9-bp could match a reference sequence located within the deleted region.

Conclusions: Two mutations of the DMD gene coexist in this family. One young child has a high disease risk. Pathogenic potential of the point mutation requires further investigation. The rare chromosomal rearrangement may be caused by short-nucleotide sequence capture or other unknown mechanisms.