De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive

被引：48

作者：

Tokita, Mari J. ^{[1
,2
]}

Braxton, Alicia A. ^{[1
,2
]}

Shao, Yunru ^{[1
,3
]}

Lewis, Andrea M. ^{[1
,3
]}

Vincent, Marie ^{[4
]}

Kury, Sebastien ^{[4
]}

Besnard, Thomas ^{[4
]}

Isidor, Bertrand ^{[4
,5
]}

Latypova, Xenia ^{[4
]}

Bezieau, Stephane ^{[4
]}

Liu, Pengfei ^{[1
,2
]}

Motter, Connie S. ^{[6
]}

Melver, Catherine Ward ^{[6
]}

Robin, Nathaniel H. ^{[7
]}

Infante, Elena M. ^{[8
,9
]}

McGuire, Marianne ^{[2
,8
,9
]}

El-Gharbawy, Areeg ^{[8
,9
]}

Littlejohn, Rebecca O. ^{[10
]}

McLean, Scott D. ^{[10
]}

Bi, Weimin ^{[1
,2
]}

Bacino, Carlos A. ^{[1
,3
]}

Lalani, Seema R. ^{[1
,3
]}

Scott, Daryl A. ^{[1
,3
,11
]}

Eng, Christine M. ^{[1
,2
,3
]}

Yang, Yaping ^{[1
,2
]}

Schaaf, Christian P. ^{[1
,3
,12
]}

Walkiewicz, Magdalena A. ^{[1
,2
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Baylor Miraca Genet Labs, Houston, TX 77021 USA

[3] Texas Childrens Hosp, Houston, TX 77030 USA

[4] Ctr Hosp Univ Nantes, Gen Med Serv, F-44093 Nantes 1, France

[5] INSERM, UMR S 957, 1 Rue Gaston Veil, F-44035 Nantes, France

[6] Akron Childrens Hosp, Genet Ctr, Akron, OH 44302 USA

[7] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA

[8] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15224 USA

[9] Childrens Hosp Pittsburgh, Pittsburgh, PA 15224 USA

[10] Childrens Hosp San Antonio, San Antonio, TX 78207 USA

[11] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA

[12] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2016年 / 99卷 / 03期

关键词：

INTERCHROMATIN GRANULE CLUSTERS; MENTAL-RETARDATION; DELETION; PHENOTYPE; 21Q22.11; DISEASE; PROTEIN; 21Q; HAPLOINSUFFICIENCY; THROMBOCYTOPENIA;

D O I：

10.1016/j.ajhg.2016.06.035

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

SON is a key component of the spliceosomal complex and a critical mediator of constitutive and alternative splicing. Additionally, SON has been shown to influence cell-cycle progression, genomic integrity, and maintenance of pluripotency in stem cell populations. The clear functional relevance of SON in coordinating essential cellular processes and its presence in diverse human tissues suggests that intact SON might be crucial for normal growth and development. However, the phenotypic effects of deleterious germline variants in SON have not been clearly defined. Herein, we describe seven unrelated individuals with de novo variants in SON and propose that deleterious variants in SON are associated with a severe multisystem disorder characterized by developmental delay, persistent feeding difficulties, and congenital malformations, including brain anomalies.

引用

页码：720 / 727

页数：8

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