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Article: Exome Sequencing and Gene Prioritization Correct Misdiagnosis in a Chinese Kindred with Familial Amyloid Polyneuropathy

TitleExome Sequencing and Gene Prioritization Correct Misdiagnosis in a Chinese Kindred with Familial Amyloid Polyneuropathy
Authors
Issue Date2016
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2016, v. 6, p. article no. 26362 How to Cite?
AbstractInherited neuropathies show considerable heterogeneity in clinical manifestations and genetic etiologies, and are therefore often difficult to diagnose. Whole-exome sequencing (WES) has been widely adopted to make definite diagnosis of unclear conditions, with proven efficacy in optimizing patients’ management. In this study, a large Chinese kindred segregating autosomal dominant polyneuropathy with incomplete penetrance was ascertained through a patient who was initially diagnosed as Charcot-Marie-Tooth disease. To investigate the genetic cause, forty-six living family members were genotyped by SNP microarrays, and one confirmed patient was subject to WES. Through systematic computational prioritization, we identified a missense mutation c.G148T in TTR gene which results in a p.V50L substitution known to cause transthyretin-related familial amyloid polyneuropathy. Co-segregation analysis and clinical follow-up confirmed the new diagnosis, which suggested new therapeutic options to the patients and informed high risk family members. This study confirms WES as a powerful tool in translational medicine, and further demostrates the practical utility of gene prioritization in narrowing the scope of causative mutation.
Persistent Identifierhttp://hdl.handle.net/10722/231247
ISSN
2015 Impact Factor: 5.228
2015 SCImago Journal Rankings: 2.073

 

DC FieldValueLanguage
dc.contributor.authorChen, H-
dc.contributor.authorZhou, X-
dc.contributor.authorWang, J-
dc.contributor.authorWang, X-
dc.contributor.authorLiu, L-
dc.contributor.authorWu, S-
dc.contributor.authorLi, T-
dc.contributor.authorChen, S-
dc.contributor.authorYang, J-
dc.contributor.authorSham, PC-
dc.contributor.authorZhu, G-
dc.contributor.authorZhang, X-
dc.contributor.authorWang, B-
dc.date.accessioned2016-09-20T05:21:46Z-
dc.date.available2016-09-20T05:21:46Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, p. article no. 26362-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/231247-
dc.description.abstractInherited neuropathies show considerable heterogeneity in clinical manifestations and genetic etiologies, and are therefore often difficult to diagnose. Whole-exome sequencing (WES) has been widely adopted to make definite diagnosis of unclear conditions, with proven efficacy in optimizing patients’ management. In this study, a large Chinese kindred segregating autosomal dominant polyneuropathy with incomplete penetrance was ascertained through a patient who was initially diagnosed as Charcot-Marie-Tooth disease. To investigate the genetic cause, forty-six living family members were genotyped by SNP microarrays, and one confirmed patient was subject to WES. Through systematic computational prioritization, we identified a missense mutation c.G148T in TTR gene which results in a p.V50L substitution known to cause transthyretin-related familial amyloid polyneuropathy. Co-segregation analysis and clinical follow-up confirmed the new diagnosis, which suggested new therapeutic options to the patients and informed high risk family members. This study confirms WES as a powerful tool in translational medicine, and further demostrates the practical utility of gene prioritization in narrowing the scope of causative mutation.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleExome Sequencing and Gene Prioritization Correct Misdiagnosis in a Chinese Kindred with Familial Amyloid Polyneuropathy-
dc.typeArticle-
dc.identifier.emailZhou, X: zhouxy@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.authoritySham, PC=rp00459-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep26362-
dc.identifier.hkuros266410-
dc.identifier.volume6-
dc.identifier.spagearticle no. 26362-
dc.identifier.epagearticle no. 26362-
dc.publisher.placeUnited Kingdom-

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