This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Bernard, G. Articles by Shevell, M. Search for Related Content PubMed PubMed Citation Articles by Bernard, G. Articles by Shevell, M. Social Bookmarking                         What's this?

Dosage Effect of a Dominant CLCN1 Mutation: A Novel Syndrome

Departments of Neurology/Neurosurgery and Pediatrics, McGill University Health Center, Montreal

Chantal Poulin, MD, FRCP C

Departments of Neurology/Neurosurgery and Pediatrics, McGill University Health Center, Montreal

Jack Puymirat, MD, FRCP C

Centre de recherche du CHUL - Université Laval, Sainte-Foy, Quebec, Canada

Damien Sternberg, MD, PhD

Service de Biochimie, Hôpital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France

Michael Shevell, MD, FRCP C

Departments of Neurology/Neurosurgery and Pediatrics, McGill University Health Center, Montreal, michael.shevell{at}muhc.mcgill.ca

Multiple mutations in the CLCN1 gene coding for the voltage-gated chloride channel have been documented to cause myotonia congenita. We report a kindred featuring an index patient who possesses 2 copies of a dominantly inherited mutated CLCN1 allele with a resulting novel phenotypic presentation. The index patient is a boy who presented initially for evaluation at the age of 5 years with a 2-year history of gait problems. Both parents and 3 male siblings were entirely well. Examination revealed a striking diffuse muscular hypertrophy, diffuse mild to moderate weakness, Gower sign, percussion, and grip myotonia. Electromyography confirmed myotonia, and molecular analysis revealed 2 copies of the T310M mutation on the CLCN1 gene. Testing of family members revealed a normal neurological examination without clinical myotonia in all and electromyographic evidence of myotonia and a single copy of the T310M mutation in both parents and 2 siblings. Our kindred is the initial demonstration of the dosage effect of a dominant mutated allele in the CLCN1 gene.

Key Words: myotonia congenita • CLCN1 • channelopathy

Journal of Child Neurology, Vol. 23, No. 2, 163-166 (2008)
DOI: 10.1177/0883073807307974


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?