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Primary adhalin deficiency as a cause of muscular dystrophy in patients with normal dystrophin
Author(s) -
Ljunggren Asa,
Duggan David,
McNally Elizabeth,
Boylan Kevin B.,
Gama Carlos H.,
Kunkel Louis M.,
Hoffman Eric P.
Publication year - 1995
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410380305
Subject(s) - muscular dystrophy , dystrophin , medicine , muscle biopsy , duchenne muscular dystrophy , compound heterozygosity , population , pediatrics , pathology , mutation , genetics , biopsy , biology , gene , environmental health
In our experience, more than half of muscular dystrophy patients show a primary dystrophinopathy. The underlying cause of muscular dystrophy in the vast majority of patients with normal dystrophin is unknown. Recently, a French family with 4 young siblings showing a muscular dystrophy of unknown progression was shown to have a primary deficiency of „adhalin,” the 50‐kd dystrophin‐associated protein. Here we report the screening of the entire adhalin coding sequence in muscle biopsy specimens from 30 muscular dystrophy patients to (1) determine whether adhalin deficiency is restricted to the French population, (2) determine the incidence of adhalin deficiency in muscular dystrophy patients, and (3) characterize the clinical features and mutations in adhalin‐deficient patients. We identified a single African‐American girl with childhood‐onset muscular dystrophy and adhalin gene mutations. We found her to be a compound heterozygote for two different mutations of the same amino acid (Arg98Cys; Arg98His), one of which was previously identified in the French family. Our results suggest that primary adhalin deficiency in patients with muscular dystrophy but normal dystrophin is relatively infrequent, and that adhalin‐deficient patients are not restricted to the French population.