Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population

Abstract Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese...

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Autores principales:	Xiaohua Fang, Xiaofan Zhu, Yin Feng, Ying Bai, Xuechao Zhao, Xiangdong Kong, Ning Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9cc517774c0942b0974957e6b31313f0
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spelling	oai:doaj.org-article:9cc517774c0942b0974957e6b31313f02021-12-02T15:14:28ZGenetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population10.1038/s41598-021-98357-22045-2322https://doaj.org/article/9cc517774c0942b0974957e6b31313f02021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98357-2https://doaj.org/toc/2045-2322Abstract Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs46, p.Arg170Cys, p.I160Ffs25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants.Xiaohua FangXiaofan ZhuYin FengYing BaiXuechao ZhaoXiangdong KongNing LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaohua Fang Xiaofan Zhu Yin Feng Ying Bai Xuechao Zhao Xiangdong Kong Ning Liu Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population
description	Abstract Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs46, p.Arg170Cys, p.I160Ffs25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants.
format	article
author	Xiaohua Fang Xiaofan Zhu Yin Feng Ying Bai Xuechao Zhao Xiangdong Kong Ning Liu
author_facet	Xiaohua Fang Xiaofan Zhu Yin Feng Ying Bai Xuechao Zhao Xiangdong Kong Ning Liu
author_sort	Xiaohua Fang
title	Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population
title_short	Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population
title_full	Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population
title_fullStr	Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population
title_full_unstemmed	Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population
title_sort	genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in chinese han population
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9cc517774c0942b0974957e6b31313f0
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Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population

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