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

BMC Medical Genetics

Huimin Xia⁵  Maria-Mercè Garcia-Barcelo¹  Paul K Tam¹  Pak C Sham¹  Stacey S Cherny²  John Nicholls³  Kenneth KY Wong⁶  Man-ting So⁶  Ruizhong Zhang⁶  Clara SM Tang⁶  Emily HM Wong⁴  Qiuming He⁵  John KL Wong⁴  Wei Liu⁵ 

[1] State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, SAR, China;Center for Genomic Sciences, The University of Hongkong, Hongkong, SAR, China;Department of Pathology, The University of Hongkong, Hongkong, SAR, China;Department of Psychiatry, The University of Hongkong, Hongkong, SAR, China;Department of Pediatric Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China;Department of Surgery, The University of Hongkong, Hongkong, SAR, China

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

Others  :  1220331
DOI  :  10.1186/s12881-015-0189-7

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

【 摘 要 】

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.

Case presentation

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

【 授权许可】

   
2015 Liu et al.

【 图 表 】

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