干旱区生态环境知识资源中心(Arid): Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster

Arid

DOI	10.1038/s41431-019-0522-2
	Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster
	Le Caignec, Cedric 1,2; Pichon, Olivier 1; Briand, Annaig 1; de Courtivron, Benoit 3; Bonnard, Christian 3,4; Lindenbaum, Pierre 5,6; Redon, Richard 5,6; Schluth-Bolard, Caroline 7,8,9; Diguet, Flavie 7; Rollat-Farnier, Pierre-Antoine 10; Sanchez-Castro, Marta 1; Vuillaume, Marie-Laure 11,12; Sanlaville, Damien 7,8,9; Duboule, Denis 13,14; Megarbane, Andre 15; Toutain, Annick 11,12
通讯作者	Le Caignec, Cedric
来源期刊	EUROPEAN JOURNAL OF HUMAN GENETICS
ISSN	1018-4813
EISSN	1476-5438
出版年	2020
卷号	28 期号:3 页码:324-332
英文摘要	The HoxD cluster is critical for vertebrate limb development. Enhancers located in both the telomeric and centromeric gene deserts flanking the cluster regulate the transcription of HoxD genes. In rare patients, duplications, balanced translocations or inversions misregulating HOXD genes are responsible for mesomelic dysplasia of the upper and lower limbs. By aCGH, whole-genome mate-pair sequencing, long-range PCR and fiber fluorescent in situ hybridization, we studied patients from two families displaying mesomelic dysplasia limited to the upper limbs. We identified microduplications including the HOXD cluster and showed that microduplications were in an inverted orientation and inserted between the HOXD cluster and the telomeric enhancers. Our results highlight the existence of an autosomal dominant condition consisting of isolated ulnar dysplasia caused by microduplications inserted between the HOXD cluster and the telomeric enhancers. The duplications likely disconnect the HOXD9 to HOXD11 genes from their regulatory sequences. This presumptive loss-of-function may have contributed to the phenotype. In both cases, however, these rearrangements brought HOXD13 closer to telomeric enhancers, suggesting that the alterations derive from the dominant-negative effect of this digit-specific protein when ectopically expressed during the early development of forearms, through the disruption of topologically associating domain structure at the HOXD locus.
类型	Article
语种	英语
国家	France ; Switzerland
开放获取类型	Green Published, Bronze
收录类别	SCI-E
WOS记录号	WOS:000515027800006
WOS关键词	KANTAPUTRA TYPE ; EXPRESSION ; TRANSLOCATION ; BREAKPOINTS ; HIERARCHY ; DOMAINS ; FAMILY ; TIME
WOS类目	Biochemistry & Molecular Biology ; Genetics & Heredity
WOS研究方向	Biochemistry & Molecular Biology ; Genetics & Heredity
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/314488
作者单位	1.CHU Nantes, Serv Genet Med, Nantes, France; 2.Univ Nantes, Nantes, France; 3.CHRU Tours, Serv Chirurg Orthoped Pediat, Tours, France; 4.Univ Francois Rabelais Tours, PRES Ctr, Val de Loire Univ, Tours, France; 5.INSERM, Inst Thorax, UMR S1087, Nantes, France; 6.CNRS, UMR 6291, Nantes, France; 7.Lyon Univ Hosp, Dept Genet, Lyon, France; 8.Claude Bernard Lyon I Univ, Lyon, France; 9.CRNL, CNRS, INSERM, UMR 5292,U1028, Lyon, France; 10.Hosp Civils Lyon, Bioinformat Cell, Lyon, France; 11.CHU Tours, Serv Genet, Hop Bretonneau, Tours, France; 12.Univ Tours, UMR 1253, iBrain, INSERM, Tours, France; 13.Univ Geneva, Lausanne, Switzerland; 14.Fed Inst Technol EPFL, Lausanne, Switzerland; 15.Inst Jerome Lejeune, Paris, France
推荐引用方式 GB/T 7714	Le Caignec, Cedric,Pichon, Olivier,Briand, Annaig,et al. Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster[J],2020,28(3):324-332.
APA	Le Caignec, Cedric.,Pichon, Olivier.,Briand, Annaig.,de Courtivron, Benoit.,Bonnard, Christian.,...&Toutain, Annick.(2020).Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster.EUROPEAN JOURNAL OF HUMAN GENETICS,28(3),324-332.
MLA	Le Caignec, Cedric,et al."Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster".EUROPEAN JOURNAL OF HUMAN GENETICS 28.3(2020):324-332.