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Article: -459C>T point mutation in 5′ non-coding region of human GJB1 gene is linked to X-linked Charcot-Marie-Tooth neuropathy

Title-459C>T point mutation in 5′ non-coding region of human GJB1 gene is linked to X-linked Charcot-Marie-Tooth neuropathy
Authors
KeywordsCharcot-Marie-Tooth
GJB1 (Connexin32)
Mutation
Neuropathy
Non-coding region
Issue Date2009
Citation
Journal Of The Peripheral Nervous System, 2009, v. 14 n. 1, p. 14-21 How to Cite?
AbstractCharcot-Marie-Tooth (CMT) neuropathy is inherited with genetic and clinical heterogeneity. The X-linked form (CMTX) is linked to mutations in the GJB1 gene. However, the genotype-phenotype correlation between variants in the non-coding region of GJB1 gene and CMTX is unclear. We found two structural variants (-459C>T and -713G>A) in the 5′ non-coding region of a transcript (Ref seq ID: NM-000166) of the GJB1 gene and explored its association with CMTX in two Chinese families. All family members who carried the -459C>T variant either were symptomatic or had abnormal electrophysiological studies compatible with CMTX, whereas all the non-symptomatic family members who had normal electrophysiological studies and 10 healthy unrelated controls did not have this variant. The other variant in the 5′-flanking region of the gene was found to be a benign polymorphism, although it had been earlier reported to be associated with CMTX in a Taiwanese family. Secondary structure prediction analysis of mutant mRNA using Mfold and RNAstructure softwares indicates that the -459C>T mutation may reduce translation efficiency of the GJB1 gene by changing its 5′-untranslated region secondary structure and abolishing the internal ribosome entry site at the initialization of its translation in Schwann cells. Our study can help clarify the causal mutations of CMTX in the non-protein coding region of GJB1. © 2009 Peripheral Nerve Society.
Persistent Identifierhttp://hdl.handle.net/10722/147598
ISSN
2014 Impact Factor: 2.758
2014 SCImago Journal Rankings: 0.916
ISI Accession Number ID
Funding AgencyGrant Number
Council, Hong KongHKU7496/04M
Donation Fund
Henry G. Leong Professorship
University of Hong Kong
Funding Information:

This project was supported by Liu Po Shan/Dr. Vincent Liu Endowment Fund for Motor Neuron Disease (S.-L.H), Research Grants Council, Hong Kong (HKU7496/04M; YQS), Donation Fund for Neurology Research (S.-L.H.) and the Henry G. Leong Professorship in Neurology (S.-L.H.). P.W.-L.H. is supported by a Postdoctoral Fellowship. M.L. is supported by Postgraduate PhD Studentship from the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Men_HK
dc.contributor.authorCheng, TSen_HK
dc.contributor.authorHo, PWLen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorMak, Wen_HK
dc.contributor.authorCheung, RTFen_HK
dc.contributor.authorRamsden, DBen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorSong, Yen_HK
dc.contributor.authorHo, SLen_HK
dc.date.accessioned2012-05-29T06:04:51Z-
dc.date.available2012-05-29T06:04:51Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of The Peripheral Nervous System, 2009, v. 14 n. 1, p. 14-21en_HK
dc.identifier.issn1085-9489en_HK
dc.identifier.urihttp://hdl.handle.net/10722/147598-
dc.description.abstractCharcot-Marie-Tooth (CMT) neuropathy is inherited with genetic and clinical heterogeneity. The X-linked form (CMTX) is linked to mutations in the GJB1 gene. However, the genotype-phenotype correlation between variants in the non-coding region of GJB1 gene and CMTX is unclear. We found two structural variants (-459C>T and -713G>A) in the 5′ non-coding region of a transcript (Ref seq ID: NM-000166) of the GJB1 gene and explored its association with CMTX in two Chinese families. All family members who carried the -459C>T variant either were symptomatic or had abnormal electrophysiological studies compatible with CMTX, whereas all the non-symptomatic family members who had normal electrophysiological studies and 10 healthy unrelated controls did not have this variant. The other variant in the 5′-flanking region of the gene was found to be a benign polymorphism, although it had been earlier reported to be associated with CMTX in a Taiwanese family. Secondary structure prediction analysis of mutant mRNA using Mfold and RNAstructure softwares indicates that the -459C>T mutation may reduce translation efficiency of the GJB1 gene by changing its 5′-untranslated region secondary structure and abolishing the internal ribosome entry site at the initialization of its translation in Schwann cells. Our study can help clarify the causal mutations of CMTX in the non-protein coding region of GJB1. © 2009 Peripheral Nerve Society.en_HK
dc.languageengen_US
dc.relation.ispartofJournal of the Peripheral Nervous Systemen_HK
dc.subjectCharcot-Marie-Toothen_HK
dc.subjectGJB1 (Connexin32)en_HK
dc.subjectMutationen_HK
dc.subjectNeuropathyen_HK
dc.subjectNon-coding regionen_HK
dc.subject.mesh5' Untranslated Regions - Geneticsen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAsian Continental Ancestry Group - Ethnologyen_US
dc.subject.meshCharcot-Marie-Tooth Disease - Genetics - Pathology - Physiopathologyen_US
dc.subject.meshChilden_US
dc.subject.meshConnexins - Geneticsen_US
dc.subject.meshDNA Mutational Analysisen_US
dc.subject.meshElectromyographyen_US
dc.subject.meshFamily Healthen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Diseases, X-Linked - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMicroscopy, Electron, Transmissionen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNeural Conduction - Genetics - Physiologyen_US
dc.subject.meshPeripheral Nerves - Pathology - Physiopathology - Ultrastructureen_US
dc.subject.meshPoint Mutation - Geneticsen_US
dc.subject.meshSequence Analysisen_US
dc.subject.meshYoung Adulten_US
dc.title-459C>T point mutation in 5′ non-coding region of human GJB1 gene is linked to X-linked Charcot-Marie-Tooth neuropathyen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, M: mxli@hku.hken_HK
dc.identifier.emailHo, PWL: hwl2002@hku.hken_HK
dc.identifier.emailCheung, RTF: rtcheung@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailSong, Y: songy@hku.hken_HK
dc.identifier.emailHo, SL: slho@hku.hken_HK
dc.identifier.authorityLi, M=rp01722en_HK
dc.identifier.authorityHo, PWL=rp00259en_HK
dc.identifier.authorityCheung, RTF=rp00434en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authoritySong, Y=rp00488en_HK
dc.identifier.authorityHo, SL=rp00240en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1529-8027.2009.00201.xen_HK
dc.identifier.pmid19335535en_HK
dc.identifier.scopuseid_2-s2.0-62849106648en_HK
dc.identifier.hkuros155728-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-62849106648&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume14en_HK
dc.identifier.issue1en_HK
dc.identifier.spage14en_HK
dc.identifier.epage21en_HK
dc.identifier.isiWOS:000264635600002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, M=17135391100en_HK
dc.identifier.scopusauthoridCheng, TS=7404082613en_HK
dc.identifier.scopusauthoridHo, PWL=25027612100en_HK
dc.identifier.scopusauthoridChan, KH=7406034963en_HK
dc.identifier.scopusauthoridMak, W=22948344000en_HK
dc.identifier.scopusauthoridCheung, RTF=7202397498en_HK
dc.identifier.scopusauthoridRamsden, DB=7102612805en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridSong, Y=7404921212en_HK
dc.identifier.scopusauthoridHo, SL=25959633500en_HK
dc.identifier.citeulike4242324-

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