Format

Send to

Choose Destination
Neurology. 2012 Jun 12;78(24):1953-8. doi: 10.1212/WNL.0b013e318259e19c. Epub 2012 May 30.

A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.

Author information

1
Medical Research Council Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, University College London, London, UK.

Abstract

OBJECTIVE:

To assess whether exon deletions or duplications in CLCN1 are associated with recessive myotonia congenita (MC).

METHODS:

We performed detailed clinical and electrophysiologic characterization in 60 patients with phenotypes consistent with MC. DNA sequencing of CLCN1 followed by multiplex ligation-dependent probe amplification to screen for exon copy number variation was undertaken in all patients.

RESULTS:

Exon deletions or duplications in CLCN1 were identified in 6% of patients with MC. Half had heterozygous exonic rearrangements. The other 2 patients (50%), with severe disabling infantile onset myotonia, were identified with both a homozygous mutation, Pro744Thr, which functional electrophysiology studies suggested was nonpathogenic, and a triplication/homozygous duplication involving exons 8-14, suggesting an explanation for the severe phenotype.

CONCLUSIONS:

These data indicate that copy number variation in CLCN1 may be an important cause of recessive MC. Our observations suggest that it is important to check for exon deletions and duplications as part of the genetic analysis of patients with recessive MC, especially in patients in whom sequencing identifies no mutations or only a single recessive mutation. These results also indicate that additional, as yet unidentified, genetic mechanisms account for cases not currently explained by either CLCN1 point mutations or exonic deletions or duplications.

PMID:
22649220
PMCID:
PMC3369509
DOI:
10.1212/WNL.0b013e318259e19c
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center