Dystrophin nonsense mutation induces different levels of exon29 skipping and leads to variable phenotypes within one BMD family

• Published in: European journal of human genetics : EJHG Vol. 8; no. 10; pp. 793 - 796
• Main Authors: Ginjaar, Ieke B, Kneppers, Alexander LJ, v d Meulen, Jan-Douwe M, Anderson, Louise VB, Bremmer-Bout, Mattie, van Deutekom, Judith CT, Weegenaar, Jitske, den Dunnen, Johan T, Bakker, Egbert
• Format: Journal Article
• Language: English
• Published: 01.10.2000
• ISSN: 1018-4813
• DOI: 10.1038/sj.ejhg.5200535

Within one X-linked muscular dystrophy family, different phenotypes for three males occurred: (1) a severely affected Becker patient with cardiomyopathy, (2) a mildly affected Becker patient, and (3) an apparently healthy male with elevated serum CK levels. In the muscle biopsy specimen of patient2 one out of four antibodies (NCL-DYS1) showed absence of dystrophin. The protein truncation test detected a truncated dystrophin for both muscle tissue and lymphocytes of this patient next to an additional near normal size fragment in muscle. Genomic sequence analysis revealed a nonsense mutation in exon29 (4148C>T) of the dystrophin gene. Sequence analysis of the mRNA fragment of the larger peptide showed skipping of exon29, restoring an open reading frame. Consequently, the epitope of the antibody NCL-DYS1 is mapped to exon29. The variable clinical features of the three relatives from healthy to severely affected therefore seems to be related to the level of skipping of exon29. This finding underscores the future potential of gene therapeutic strategies aimed at inducing exon skipping in Duchenne muscular dystrophy, to generate a much milder disease. European Journal of Human Genetics (2000) 8, 793-796.