干旱区生态环境知识资源中心(Arid): Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD

Arid

DOI	10.1210/js.2019-00306
	Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD
	Buonocore, Federica; Clifford-Mobley, Oliver; King, Tom F. J.; Striglioni, Niccolo; Man, Elim; Suntharalingham, Jenifer P.; del Valle, Ignacio; Lin, Lin; Lagos, Carlos F.; Rumsby, Gill; Conway, Gerard S.; Achermann, John C.
通讯作者	Achermann, JC
来源期刊	JOURNAL OF THE ENDOCRINE SOCIETY
EISSN	2472-1972
出版年	2019
卷号	3 期号:12 页码:2341-2360
英文摘要	Context: The genetic basis of human sex development is slowly being elucidated, and >40 different genetic causes of differences (or disorders) of sex development (DSDs) have now been reported. However, reaching a specific diagnosis using traditional approaches can be difficult, especially in adults where limited biochemical data may be available. Objective: We used a targeted next-generation sequencing approach to analyze known and candidate genes for DSDs in individuals with no specific molecular diagnosis. Participants and Design: We studied 52 adult 46,XY women attending a single-center adult service, who were part of a larger cohort of 400 individuals. Classic conditions such as17 beta-hydroxysteroid dehydrogenase deficiency type 3, 5a-reductase deficiency type 2, and androgen insensitivity syndrome were excluded. The study cohort had broad working diagnoses of complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25), a group that included partial gonadal dysgenesis and those with a broad "partial androgen insensitivity syndrome" label. Targeted sequencing of 180 genes was undertaken. Results: Overall, a likely genetic cause was found in 16 of 52 (30.8%) individuals (22.2% CGD, 40.0% pvDSD). Pathogenic variants were found in sex-determining region Y (SRY; n = 3), doublesex and mab3-related transcription factor 1 (DMRT1; n = 1), NR5A1/steroidogenic factor-1 (SF-1) (n = 1), and desert hedgehog (DHH; n = 1) in the CGD group, and in NR5A1 (n = 5), DHH (n = 1), and DEAH-box helicase 37 (DHX37; n = 4) in the pvDSD group. Conclusions: Reaching a specific diagnosis can have clinical implications and provides insight into the role of these proteins in sex development. Next-generation sequencing approaches are invaluable, especially in adult populations or where diagnostic biochemistry is not possible.
英文关键词	desert hedgehog DSD DHX37 sex determination SRY steroidogenic factor-1
类型	Article
语种	英语
开放获取类型	DOAJ Gold, Green Published
收录类别	ESCI
WOS记录号	WOS:000507641300014
WOS关键词	SEX DEVELOPMENT DSD ; FACTOR-I SF-1 ; DESERT-HEDGEHOG ; GONADAL-DYSGENESIS ; MOLECULAR-DYNAMICS ; DISORDERS ; PROTEIN ; MUTATIONS ; DIAGNOSIS ; EXPRESSION
WOS类目	Endocrinology & Metabolism
WOS研究方向	Endocrinology & Metabolism
来源机构	University of London
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/334056
作者单位	[Buonocore, Federica; Striglioni, Niccolo; Man, Elim; Suntharalingham, Jenifer P.; del Valle, Ignacio; Lin, Lin; Achermann, John C.] UCL, UCL Great Ormond St Inst Child Hlth, Genet & Genom Med, London WC1N 1EH, England; [Clifford-Mobley, Oliver; Rumsby, Gill] Univ Coll London Hosp, Clin Biochem, London W1T 4EU, England; [King, Tom F. J.; Conway, Gerard S.] Univ Coll London Hosp, Reprod Med Unit, London NW1 2PG, England; [Lagos, Carlos F.] Univ San Sebastian, Fac Med & Ciencia, Chem Biol & Drug Discovery Lab, Santiago 7510157, Chile
推荐引用方式 GB/T 7714	Buonocore, Federica,Clifford-Mobley, Oliver,King, Tom F. J.,et al. Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD[J]. University of London,2019,3(12):2341-2360.
APA	Buonocore, Federica.,Clifford-Mobley, Oliver.,King, Tom F. J..,Striglioni, Niccolo.,Man, Elim.,...&Achermann, John C..(2019).Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD.JOURNAL OF THE ENDOCRINE SOCIETY,3(12),2341-2360.
MLA	Buonocore, Federica,et al."Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD".JOURNAL OF THE ENDOCRINE SOCIETY 3.12(2019):2341-2360.