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期刊论文 2

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2007 1

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Mutation analysis of KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes in Chinese patients with long QT syndrome

DU Rong, TIAN Li, YUAN Guohui, LI Jin, REN Faxin, GUI Le, LI Wei, ZHANG Shouyan, KANG Cailian, YANG Junguo

《医学前沿（英文）》 2007年 第1卷 第3期   页码 312-315 doi: 10.1007/s11684-007-0060-0

摘要： Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies, which cause syncope and sudden death. Inherited LQTS is represented by the autosomal dominant Romano-ward syndrome (RWS), which is not accompanied by congenital deafness, and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS), which is accompanied by congenital deafness. The LQTS-causing mutations have been reported in patients and families from Europe, North America and Japan. Few genetic studies have been carried out in families with JLNS from China. This study investigates the molecular pathology in four families with LQTS (including a family with JLNS) in the Chinese population. Polymerase chain reaction and DNA sequencing were used to screen for , , , and mutation. A missense mutation G314S in an RWS family was identified, and a single nucleotide polymorphism (SNP) G643S was indentified in the of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in of the patients. Our data provide useful information for the identification of polymorphisms and mutations related to LQTS and the Brugada Syndrome (BS) in Chinese populations.

关键词： recessive Jervell     LQTS-causing     population     autosomal dominant     syndrome    

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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in , , and

《医学前沿（英文）》 doi: 10.1007/s11684-023-1006-x

摘要： Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants in TMEM141 (c.270G>A, p.Trp90*), DDHD2 (c.411+767_c.1249-327del), and LHFPL5 (c.250delC, p.Leu84*) were identified. A Tmem141p.Trp90*/p.Trp90* mouse model was generated. Behavioral studies showed impairments in learning ability and motor coordination. Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells. Transmission electron microscopy showed abnormal mitochondrial morphology. Furthermore, studies on a human in vitro neuronal model (SH-SY5Y cells) with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function, possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model. Conclusively, panoramic variation analysis revealed that multilocus genomic variations of TMEM141, DDHD2, and LHFPL5 together caused variable phenotypes in patient. Notably, the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder     autosomal recessive intellectual disability     consanguinity     spastic paraplegia     hearing loss     TMEM141    

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标题 作者 时间 类型 操作

Mutation analysis of KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes in Chinese patients with long QT syndrome

DU Rong, TIAN Li, YUAN Guohui, LI Jin, REN Faxin, GUI Le, LI Wei, ZHANG Shouyan, KANG Cailian, YANG Junguo

期刊论文

Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in , , and

期刊论文