A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.
Authors
Murphy, Sinéad MPolke, James
Manji, Hadi
Blake, Julian
Reiniger, Lilla
Sweeney, Mary
Houlden, Henry
Brandner, Sebastian
Reilly, Mary M
Affiliation
MRC Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK. sinead.murphy@uclh.nhs.ukIssue Date
2011-03MeSH
5' Untranslated RegionsAdult
Age of Onset
Aged
Base Sequence
Charcot-Marie-Tooth Disease
Connexins
Electrophysiology
Female
Genetic Diseases, X-Linked
Humans
Male
Middle Aged
Molecular Sequence Data
Mutation
Pedigree
Young Adult
Metadata
Show full item recordCitation
A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease. 2011, 16 (1):65-70 J. Peripher. Nerv. Syst.Journal
Journal of the peripheral nervous system : JPNSDOI
10.1111/j.1529-8027.2011.00321.xPubMed ID
21504505Abstract
X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene which codes for connexin 32 (CX32). CX32 has three tissue-specific promoters, P1 which is specific for liver and pancreas, P1a specific for liver, oocytes and embryonic stem cells, and P2 which is nerve-specific. Over 300 mutations have been described in GJB1, spread throughout the coding region. We describe two families with X-linked inheritance and a phenotype consistent with CMT1X who did not have mutations in the GJB1 coding region. The non-coding region of GJB1 was sequenced and an upstream exon-splicing variant found at approximately - 373G>A which segregated with the disease in both families and was not present in controls. This substitution is located at the last base of the nerve-specific 5'UTR and thus may disrupt splicing of the nerve-specific transcript. Online consensus splice-site programs predict a reduced score for the mutant sequence vs. the normal sequence. It is likely that other mutations within the GJB1 non-coding regions account for the CMT1X families who do not have coding region mutations.Item Type
ArticleLanguage
enISSN
1529-8027ae974a485f413a2113503eed53cd6c53
10.1111/j.1529-8027.2011.00321.x
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