title: Chinese family with diffuse oesophageal leiomyomatosis: a new COL4A5/COL4A6 deletion and a case of gonosomal mosaicism.
abstract: BACKGROUND
  Diffuse 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.
  
  
  METHODS
  We 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.
  
  
  CONCLUSIONS
  This is the first report of gonadosomal mosaicism associated to DOL-AS.
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, China. liuwei19610624@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China. wkljohn@hku.hk.
authors.forename: John K L
authors.initials: JK
authors.lastname: Wong
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, China. 506240623@qq.com.
authors.forename: Qiuming
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China. emilyhmwong@gmail.com.
authors.forename: Emily H M
authors.initials: EH
authors.lastname: Wong
authors.affiliation: Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China. claratsm@gmail.com.|Department of Surgery, The University of Hongkong, Hongkong, SAR, China. claratsm@gmail.com.
authors.forename: Clara S M
authors.initials: CS
authors.lastname: Tang
authors.affiliation: Department of Surgery, The University of Hongkong, Hongkong, SAR, China. h1094156@hku.hk.
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The University of Hongkong, Hongkong, SAR, China. jaymtso@hku.hk.
authors.forename: Man-Ting
authors.initials: MT
authors.lastname: So
authors.affiliation: Department of Surgery, The University of Hongkong, Hongkong, SAR, China. kkywong@hku.hk.
authors.forename: Kenneth K Y
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Department of Pathology, The University of Hongkong, Hongkong, SAR, China. nicholls@pathology.hku.hk.
authors.forename: John
authors.initials: J
authors.lastname: Nicholls
authors.affiliation: Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China. cherny@hku.hk.|Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China. cherny@hku.hk.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China. pcsham@hku.hk.|Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China. pcsham@hku.hk.|Centre for Reproduction, Development, and Growth of the Li Ka Shing Faculty of Medicine, Hong Kong, SAR, China. pcsham@hku.hk.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, SAR, China. pcsham@hku.hk.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Department of Surgery, The University of Hongkong, Hongkong, SAR, China. paultam@hku.hk.|Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China. paultam@hku.hk.|Centre for Reproduction, Development, and Growth of the Li Ka Shing Faculty of Medicine, Hong Kong, SAR, China. paultam@hku.hk.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, SAR, China. paultam@hku.hk.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Tam
authors.affiliation: Department of Surgery, The University of Hongkong, Hongkong, SAR, China. mmgarcia@hku.hk.|Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China. mmgarcia@hku.hk.|Centre for Reproduction, Development, and Growth of the Li Ka Shing Faculty of Medicine, Hong Kong, SAR, China. mmgarcia@hku.hk.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, SAR, China. mmgarcia@hku.hk.
authors.forename: Maria-Mercè
authors.initials: MM
authors.lastname: Garcia-Barcelo
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, China. huiminxia@hotmail.com.
authors.forename: Huimin
authors.initials: H
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D044466:Asian People; D041321:Chromosomes, Human, X; D024141:Collagen Type IV / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005190:Family; D005260:Female; D017353:Gene Deletion; D006801:Humans; D018231:Leiomyomatosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D009030:Mosaicism; D009394:Nephritis, Hereditary / Q000235:genetics / Q000473:pathology; D012729:Sex Chromosome Aberrations
chemical_list: C478159:COL4A5 protein, human; C559044:COL4A6 protein, human; D024141:Collagen Type IV