title: Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy.
abstract: We have analysed the results of clinical assessment, X-inactivation status, deletion screening and dystrophin analysis in eight manifesting carriers of Duchenne and Becker muscular dystrophy (DMD and BMD). Only two had a prior family history of X-linked muscle disease, all had normal karyotypes and none were twins. Presentation varied from 2 to 25 yr and progression varied from a DMD-like severity to a very mild BMD-like course. In one girl the initial symptoms were restricted to learning difficulties. Where methods for assessing X-inactivation were informative, three patients showed an abnormal pattern. However, in one patient, the obligate carrier daughter of a BMD patient who had presented at the age of 2 yr, X-inactivation appeared normal in lymphocytes and muscle. While dystrophin analysis seems to be reliable in identifying manifesting carriers of DMD and BMD, the relationship between X-inactivation status, dystrophin analysis and phenotype is not simple.
authors.affiliation: Department of Human Genetics, University of Newcastle upon Tyne, U.K.
authors.forename: K M
authors.initials: KM
authors.lastname: Bushby
authors.forename: J A
authors.initials: JA
authors.lastname: Goodship
authors.forename: L V
authors.initials: LV
authors.lastname: Nicholson
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: I D
authors.initials: ID
authors.lastname: Haggerty
authors.forename: D
authors.initials: D
authors.lastname: Gardner-Medwin
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016189:Dystrophin / Q000032:analysis*; D005190:Family; D005260:Female; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000473:pathology*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D016133:Polymerase Chain Reaction; D014960:X Chromosome
chemical_list: D016189:Dystrophin