Variable phenotypes associated with mutations in DOK7.

Abstract:

: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 1263insC 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.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Anderson JA,Ng JJ,Bowe C,McDonald C,Richman DP,Wollmann RL,Maselli RA

doi

10.1002/mus.20944

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

448-56

issue

4

eissn

0148-639X

issn

1097-4598

journal_volume

37

pub_type

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