caa a22 4500 469044683 CHVBK 20180323132821.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF01799613 doi (NATIONALLICENCE)springer-10.1007/BF01799613 Worton R. Department of Genetics and Research Institute, Hospital for Sick Children, Canada aut Duchenne muscular dystrophy: Gene and gene product; mechanism of mutation in the gene [Elektronische Daten] [R. Worton] Summary: The X-linked gene responsible for Duchenne muscular dystrophy encodes dystrophin, a high-molecular-weight cytoskeletal protein. Studies in several laboratories have revealed deletion of one or more exons in 60% of affected boys; quantitative analysis in our laboratory has detected duplication of exons in another 6%. The severe Duchenne phenotype is associated with deletions or duplications that shift the reading frame of the message, whereas the milder Becker muscular dytrophy is associated with deletions or duplications that maintain the reading frame. Patients who have neither deletion nor duplication may have nonsense mutations, one of which has been detected by predicting the site of the mutation from the size of the truncated protein. Rare females with the disease have a translocation that disrupts the dystrophin gene on one X chromosome and causes non-random inactivation of the normal X, resulting in the expression of the disease. The high frequency of new mutation provides an opportunity to study the mechanism of chromosomal rearrangement that is characteristic of the disease. Our laboratory has focused on the translocations in females and on duplications in affected males. The X-autosome translocations of affected females are allde novo events that originated in the paternal set of chromosomes. Molecular characterization of the translocation junctions revealed reciprocal translocation with both deletion and addition of nucleotides at the junction, suggestive of a breakage and reunion mechanism. Duplications studied to date are all tandem in nature and sequence analysis of duplication junctions has revealed both homologous and non-homologous recombination. Marker segregation analysis has revealed that five out of five duplications originated in a single X chromosome of one of the maternal grandparents, suggesting that the recombination event is unequal sister chromatid exchange. SSIEM and Kluwer Academic Publishers, 1992 Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/4(1992-07-01), 539-550 0141-8955 15:4<539 1992 15 10545 https://doi.org/10.1007/BF01799613 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01799613 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Worton R. Department of Genetics and Research Institute, Hospital for Sick Children, Canada aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/4(1992-07-01), 539-550 0141-8955 15:4<539 1992 15 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer