A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP

被引：254

作者：

Helsmoortel, Celine ^{[1
]}

Vulto-van Silfhout, Anneke T. ^{[2
]}

Coe, Bradley P. ^{[3
,4
]}

Vandeweyer, Geert ^{[1
,5
]}

Rooms, Liesbeth ^{[1
]}

van den Ende, Jenneke ^{[6
]}

Schuurs-Hoeijmakers, Janneke H. M. ^{[2
]}

Marcelis, Carlo L. ^{[2
]}

Willemsen, Marjolein H. ^{[2
]}

Vissers, Lisenka E. L. M. ^{[2
]}

Yntema, Helger G. ^{[2
]}

Bakshi, Madhura ^{[7
]}

Wilson, Meredith ^{[8
]}

Witherspoon, Kali T. ^{[3
,4
]}

Malmgren, Helena ^{[9
]}

Nordgren, Ann ^{[9
]}

Anneren, Goran ^{[10
]}

Fichera, Marco ^{[11
,12
]}

Bosco, Paolo ^{[13
]}

Romano, Corrado ^{[14
]}

de Vries, Bert B. A. ^{[2
,15
]}

Kleefstra, Tjitske ^{[2
,15
]}

Kooy, R. Frank ^{[1
]}

Eichler, Evan E. ^{[3
,4
]}

Van der Aa, Nathalie ^{[1
,6
]}

机构：

[1] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium

[2] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Dis, Nijmegen Ctr Mol Life Sci,Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[3] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA

[4] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

[5] Univ Antwerp, Dept Math & Comp Sci, Biomed Informat Res Ctr Antwerpen Biomina, Edegem, Belgium

[6] Univ Antwerp Hosp, Antwerp, Belgium

[7] Westmead Hosp, Dept Med Genet, Sydney, NSW, Australia

[8] Childrens Hosp, Dept Clin Genet, Westmead, NSW, Australia

[9] Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, Stockholm, Sweden

[10] Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden

[11] IRCCS, Assoc Oasi Maria Santissima, Neurol Unit, Troina, Italy

[12] Univ Catania, Catania, Italy

[13] IRCCS, Assoc Oasi Maria Santissima, Lab Cytogenet, Troina, Italy

[14] IRCCS, Assoc Oasi Maria Santissima, Unit Pediat & Med Genet, Troina, Italy

[15] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands

来源：

NATURE GENETICS | 2014年 / 46卷 / 04期

关键词：

DEPENDENT NEUROPROTECTIVE PROTEIN; CHROMATIN-REMODELING COMPLEX; GENES; HAPLOINSUFFICIENCY; COMPONENTS; PHENOTYPE; GALAXY; ROLES; NAP;

D O I：

10.1038/ng.2899

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities(1), a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile- X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in nextgeneration sequencing, for the large majority of cases no molecular diagnosis can be established(2-7). Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/ SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD- associated genes known to date.

引用

页码：380 / +

页数：6

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