Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis

IMR OpenIR

	Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis
其他题名	Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis
	Wang Rongrong 1; Yang Shuanghao 2; Xu Ming 2; Huang Jia 3; Liu Hongyan 4; Gu Weiyue 2; Zhang Xue 1
	2018
发表期刊	SCIENCE CHINA-LIFE SCIENCES
ISSN	1674-7305
卷号	61 期号:8 页码:947-953
摘要	Hereditary spherocytosis (HS), the most common cause of congenital hemolytic anemia, is caused by deficiency of the erythrocyte membrane proteins. Five causative genes (ANK1, SPTB, SPTA1, SLC4A1, and EPB42) have been identified. To date, molecular genetic studies have been performed in different populations, including the American, European, Brazilian, Japanese and Korean populations, whereas only a few studies have been described in the Chinese population. Here, by reanalysis of the exome data, we revealed causative mutations and established a definitive diagnosis of HS in all 38 Chinese families. We found 34 novel mutations and four reported mutations in three known HS-causing genes-17 in ANK1, 17 in SPTB and four in SLC4A1, suggesting that ANK1 and SPTB are the major genes in Chinese patients with HS. All of the ANK1 or SPTB mutations, scattered throughout the entire genes, are non-recurrent; and most of them are null mutations, which might cause HS via a haploinsufficiency mechanism. De novo mutations in ANK1 or SPTB often occur with an unexpected high frequency (87.5% and 64.2%, respectively). Our study updates our knowledge about the genetic profile of HS in Chinese and shows that family-based, especially parent-offspring trio, sequencing analysis can help to increase the diagnostic power and improve diagnostic efficiency.
其他摘要	Hereditary spherocytosis （HS）, the most common cause of congenital hemolytic anemia, is caused by deficiency of the ery- throcyte membrane proteins. Five causative genes （ANK1, SPTB, SPTA1, SLC4AI, and EPB42） have been identified. To date, molecular genetic studies have been performed in different populations, including the American, European, Brazilian, Japanese and Korean populations, whereas only a few studies have been described in the Chinese population. Here, by reanalysis of the exome data, we revealed causative mutations and established a definitive diagnosis of HS in all 38 Chinese families. We found 34 novel mutations and four reported mutations in three known HS-causing genes--17 in ANK1, 17 in SPTB and four in SLC4A1, suggesting that ANK1 and SPTB are the major genes in Chinese patients with HS. All of the ANK1 or SPTB mutations, scattered throughout the entire genes, are non-recurrent; and most of them are null mutations, which might cause HS via a hap-loinsufficiency mechanism. De novo mutations in ANK1 or SPTB often occur with an unexpected high frequency （87.5% and 64.2%, respectively）. Our study updates our knowledge about the genetic profile of HS in Chinese and shows that family-based, especially parent-offspring trio, sequencing analysis can help to increase the diagnostic power and improve diagnostic efficiency.
关键词	RED-CELL MEMBRANE HEMATOLOGICALLY IMPORTANT MUTATIONS RENAL TUBULAR-ACIDOSIS HEMOLYTIC-ANEMIA BETA-SPECTRIN CYTOPLASMIC DOMAIN BAND-3 DEFICIENCY DISORDERS ANKYRIN VARIANTS hereditary spherocytosis mutation ANK1 SPTB SLC4A1 whole-exome sequencing
收录类别	CSCD
语种	英语
资助项目	[National Key Research and Development Program of China] ; [CAMS Innovation Fund for Medical Sciences] ; [National Natural Science Foundation of China (NSFC)] ; [Beijing Municipal Science and Technology Commission] ; [Medical Science and Technology Research Projects of Henan Provincial Health Bureau] ; [Scientific and Technological Projects of the Technology Bureau of Henan Provincial Technology]
CSCD记录号	CSCD:6343154
引用统计	被引频次：11[CSCD] [CSCD记录]
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/152380
专题	中国科学院金属研究所
作者单位	1.中国医学科学院 2.Joy Orient Translat Med Res Ctr Co Ltd, Beijing 100176, Peoples R China 3.中国科学院金属研究所 4.Henan Univ, Zhengzhou Univ, Henan Prov Peoples Hosp, Med Genet Institute,Peoples Hosp, Zhengzhou 450000, Henan, Peoples R China
推荐引用方式 GB/T 7714	Wang Rongrong,Yang Shuanghao,Xu Ming,et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis[J]. SCIENCE CHINA-LIFE SCIENCES,2018,61(8):947-953.
APA	Wang Rongrong.,Yang Shuanghao.,Xu Ming.,Huang Jia.,Liu Hongyan.,...&Zhang Xue.(2018).Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis.SCIENCE CHINA-LIFE SCIENCES,61(8),947-953.
MLA	Wang Rongrong,et al."Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis".SCIENCE CHINA-LIFE SCIENCES 61.8(2018):947-953.