Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family

• Published in: American journal of medical genetics Vol. 49; no. 3; p. 323
• Main Authors: Hoop, R C, Russo, L S, Riconda, D L, Schwartz, L S, Hoffman, E P
• Format: Journal Article
• Language: English
• Published: United States 01.02.1994
• Subjects: Adolescent; Child; DNA Mutational Analysis; Dystrophin - genetics; Female; Gene Deletion; Genetic Linkage; Haplotypes; Heterozygote; Humans; Male; Muscular Dystrophies - genetics; Oligodeoxyribonucleotides - genetics; Pedigree; Recombination, Genetic; Repetitive Sequences, Nucleic Acid
• DOI: 10.1002/ajmg.1320490316
• ISSN: 0148-7299

Two male cousins with Duchenne muscular dystrophy were found to have different maternal dystrophin gene haplotypes and different deletion mutations. One propositus showed two noncontiguous deletions--one in the 5', proximal deletional hotspot region, and the other in the 3', more distal deletional hotspot region. The second propositus showed only the 5' deletion. Using multiple fluorescent exon dosage and fluorescent multiplex CA repeat linkage analyses, we show that the mother of each propositus carries both deletions on the same grandmaternal X chromosome. This paradox is explained by a single recombinational event between the 2 deleted regions of one of the carrier's dystrophin genes, giving rise to a son with a partially "repaired" gene retaining only the 5' deletion.