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dc.contributor.authorMurphy, Sinéad M
dc.contributor.authorPolke, James
dc.contributor.authorManji, Hadi
dc.contributor.authorBlake, Julian
dc.contributor.authorReiniger, Lilla
dc.contributor.authorSweeney, Mary
dc.contributor.authorHoulden, Henry
dc.contributor.authorBrandner, Sebastian
dc.contributor.authorReilly, Mary M
dc.date.accessioned2012-12-05T11:40:12Z
dc.date.available2012-12-05T11:40:12Z
dc.date.issued2011-03
dc.identifier.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.en_GB
dc.identifier.issn1529-8027
dc.identifier.pmid21504505
dc.identifier.doi10.1111/j.1529-8027.2011.00321.x
dc.identifier.urihttp://hdl.handle.net/10147/254554
dc.description.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.
dc.language.isoenen
dc.publisherJournal of the peripheral nervous system : JPNSen_GB
dc.rightsArchived with thanks to Journal of the peripheral nervous system : JPNSen_GB
dc.subject.mesh5' Untranslated Regions
dc.subject.meshAdult
dc.subject.meshAge of Onset
dc.subject.meshAged
dc.subject.meshBase Sequence
dc.subject.meshCharcot-Marie-Tooth Disease
dc.subject.meshConnexins
dc.subject.meshElectrophysiology
dc.subject.meshFemale
dc.subject.meshGenetic Diseases, X-Linked
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshMolecular Sequence Data
dc.subject.meshMutation
dc.subject.meshPedigree
dc.subject.meshYoung Adult
dc.titleA novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.en_GB
dc.typeArticleen
dc.contributor.departmentMRC Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK. sinead.murphy@uclh.nhs.uken_GB
dc.identifier.journalJournal of the peripheral nervous system : JPNSen_GB
dc.description.provinceLeinsteren
html.description.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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