Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome

Abstract. Kabuki syndrome (KS) is a rare congenital mental retardation condition characterized by facial dysmorphia, visceral and skeletal malformations, and developmental delay. The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases. In this study,...

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Main Authors:	Weihui Shi, Yiyao Chen, Songchang Chen, Shuyuan Li, Chunxin Chang, Lanlan Zhang, Hongjun Fei, Hefeng Huang, Junyu Zhang, Chenming Xu
Format:	Article
Language:	English
Published:	Wolters Kluwer Health 2018-12-01
Series:	Journal of Bio-X Research
Online Access:	http://journals.lww.com/10.1097/JBR.0000000000000022

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spelling	doaj-d5526d18e4ab40a2860849aa732a4c7d2020-11-25T03:16:42ZengWolters Kluwer HealthJournal of Bio-X Research2096-56722577-35852018-12-011314014610.1097/JBR.0000000000000022201812000-00007Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndromeWeihui ShiYiyao ChenSongchang ChenShuyuan LiChunxin ChangLanlan ZhangHongjun FeiHefeng HuangJunyu ZhangChenming XuAbstract. Kabuki syndrome (KS) is a rare congenital mental retardation condition characterized by facial dysmorphia, visceral and skeletal malformations, and developmental delay. The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases. In this study, a Chinese woman, presenting with characteristic facial features of KS, came for pre-pregnancy consultation. We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling. Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants, respectively. The candidate variant was verified by Sanger sequencing. We identified a novel de novo KDM6A pathogenic variant (c.3521G>A) in the woman, which was in line with the Face2Gene analysis result. Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A. Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.http://journals.lww.com/10.1097/JBR.0000000000000022
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Weihui Shi Yiyao Chen Songchang Chen Shuyuan Li Chunxin Chang Lanlan Zhang Hongjun Fei Hefeng Huang Junyu Zhang Chenming Xu
spellingShingle	Weihui Shi Yiyao Chen Songchang Chen Shuyuan Li Chunxin Chang Lanlan Zhang Hongjun Fei Hefeng Huang Junyu Zhang Chenming Xu Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome Journal of Bio-X Research
author_facet	Weihui Shi Yiyao Chen Songchang Chen Shuyuan Li Chunxin Chang Lanlan Zhang Hongjun Fei Hefeng Huang Junyu Zhang Chenming Xu
author_sort	Weihui Shi
title	Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome
title_short	Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome
title_full	Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome
title_fullStr	Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome
title_full_unstemmed	Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome
title_sort	integrated facial analysis and targeted sequencing identifies a novel kdm6a pathogenic variant resulting in kabuki syndrome
publisher	Wolters Kluwer Health
series	Journal of Bio-X Research
issn	2096-5672 2577-3585
publishDate	2018-12-01
description	Abstract. Kabuki syndrome (KS) is a rare congenital mental retardation condition characterized by facial dysmorphia, visceral and skeletal malformations, and developmental delay. The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases. In this study, a Chinese woman, presenting with characteristic facial features of KS, came for pre-pregnancy consultation. We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling. Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants, respectively. The candidate variant was verified by Sanger sequencing. We identified a novel de novo KDM6A pathogenic variant (c.3521G>A) in the woman, which was in line with the Face2Gene analysis result. Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A. Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.
url	http://journals.lww.com/10.1097/JBR.0000000000000022
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Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome

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