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Variable phenotypes associated with mutations in DOK7
Author(s) -
Anderson Jennifer A.,
Ng Jarae J.,
Bowe Constance,
Mcdonald Craig,
Richman David P.,
Wollmann Robert L.,
Maselli Ricardo A.
Publication year - 2008
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20944
Subject(s) - phenotype , congenital myasthenic syndrome , mutation , biology , genetics , neuromuscular junction , genotype , gene , neuroscience
Many patients with the limb‐girdle variant of congenital myasthenic syndrome (CMS) possess mutations in the human Dok‐7 gene ( DOK7 ). We identified six unrelated CMS patients with DOK7 mutations. Two patients, one mildly and the other moderately affected, were homozygous for the previously described 1263ins C mutation. The common 1124_1127dupTGCC mutation was detected in the other four patients, whose clinical phenotypes range from mildly to severely affected. This striking phenotypic heterogeneity found both within and between mutational classes is made more compelling by data from our electrophysiological studies and electron microscopy of the neuromuscular junction (NMJ). Indeed, several aspects of the physiological and morphometric data do not correlate with genotype or severity of clinical phenotype. Overall, our study corroborates the findings of others and provides an additional demonstration of the considerable phenotypic variability associated with CMS due to DOK7 mutations. Muscle Nerve, 2008