Chinese family with diffuse oesophageal leiomyomatosis: a new COL4A5/COL4A6 deletion and a case of gonosomal mosaicism

BMC Medical Genetics

Case Report

John Nicholls¹  Wei Liu²  Huimin Xia²  Qiuming He²  John KL Wong³  Emily HM Wong³  Stacey S Cherny⁴  Pak C Sham⁵  Clara SM Tang⁶  Kenneth KY Wong⁷  Man-ting So⁷  Ruizhong Zhang⁷  Paul K Tam⁸  Maria-Mercè Garcia-Barcelo⁸ 

[1] Department of Pathology, The University of Hongkong, Hongkong, SAR, China;Department of Pediatric Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China;Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China;Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China;Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China;Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China;Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China;Centre for Reproduction, Development, and Growth of the Li Ka Shing Faculty of Medicine, Hong Kong, SAR, China;State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, SAR, China;Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China;Department of Surgery, The University of Hongkong, Hongkong, SAR, China;Department of Surgery, The University of Hongkong, Hongkong, SAR, China;Department of Surgery, The University of Hongkong, Hongkong, SAR, China;Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China;Centre for Reproduction, Development, and Growth of the Li Ka Shing Faculty of Medicine, Hong Kong, SAR, China;State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, SAR, China;

关键词: Isolated diffuse oesophageal leiomyomatosis;    Whole exome sequencing;    Copy number variation;    COL4A5;    COL4A6;    Gonosomal mosaicism;   

DOI  :  10.1186/s12881-015-0189-7

 received in 2014-11-17, accepted in 2015-06-15,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundDiffuse oesophageal leiomyomatosis (DOL) is a rare disorder characterized by tumorous overgrowth of the muscular wall of the oesophagus. DOL is present in 5 % of Alport syndrome (AS) patients. AS is a rare hereditary disease that involves varying degrees of hearing impairment, ocular changes and progressive glomerulonephritis leading to renal failure. In DOL-AS patients, the genetic defect consists of a deletion involving the COL4A5 and COL4A6 genes on the X chromosome.Case presentationWe report a two-generation family (4 individuals; parents and two children, one male and one female) with two members (mother and son) affected with oesophageal leiomyomatosis. Signs of potential renal failure, which characterizes AS, were only apparent in the index patient (son) 2 years and three months after the initial diagnosis of DOL. Blood DNA from the four family members were submitted to exome sequencing and array genotyping to perform a genome wide screening for disease causal single nucleotide (SN) and copy number (CN) variations. Analyses revealed a new 40kb deletion encompassing from intron 2 of COL4A5 to intron 1 of COL4A6 at Xq22.3. The breakpoints were also identified. Possible confounding pathogenic exonic variants in genes known to be involved in other extracellular matrices disorders were also shared by the two affected individuals. Meticulous analysis of the maternal DNA revealed a case of gonosomal mosaicism.ConclusionsThis is the first report of gonadosomal mosaicism associated to DOL-AS

【 授权许可】

Unknown   
© Liu et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.