title: 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.
authors.affiliation: Department of Neurology, University of California at Davis, Davis, CA 95618, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Anderson
authors.forename: Jarae J
authors.initials: JJ
authors.lastname: Ng
authors.forename: Constance
authors.initials: C
authors.lastname: Bowe
authors.forename: Craig
authors.initials: C
authors.lastname: McDonald
authors.forename: David P
authors.initials: DP
authors.lastname: Richman
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wollmann
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Maselli
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D004252:DNA Mutational Analysis; D019054:Evoked Potentials, Motor; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype
chemical_list: C511692:DOK7 protein, human; D009124:Muscle Proteins