A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.
AuthorsMurphy, Sinéad M
Reilly, Mary M
AffiliationMRC Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK. email@example.com
MeSH5' Untranslated Regions
Age of Onset
Genetic Diseases, X-Linked
Molecular Sequence Data
MetadataShow full item record
CitationA 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.
JournalJournal of the peripheral nervous system : JPNS
AbstractX-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.
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- Issue date: 2009 Mar
- Mild form of Charcot-Marie-Tooth type 1X disease caused by a novel Cys179Gly mutation in the GJB1/Cx32 gene.
- Authors: Moszyńka I, Kabzińska D, Kochański A
- Issue date: 2009 Oct
- [Two novel mutations of GJB1 gene associated with typical X-linked Charcot-Marie-Tooth disease].
- Authors: Qiao XH, Li YX, Chang XZ, Luan XH, Chen B, Bu DF, Yuan Y
- Issue date: 2009 Dec 22
- Gap junction beta 1 (GJB1) gene mutations in Italian patients with X-linked Charcot-Marie-Tooth disease.
- Authors: Mandich P, Grandis M, Geroldi A, Acquaviva M, Varese A, Gulli R, Ciotti P, Bellone E
- Issue date: 2008
- Molecular genetics of X-linked Charcot-Marie-Tooth disease.
- Authors: Kleopa KA, Scherer SS
- Issue date: 2006