A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion

被引：37

作者：

Franco, Luis M. ^{[1
]}

de Ravel, Thomy ^{[2
]}

Graham, Brett H. ^{[1
]}

Frenkel, Stephanie M. ^{[3
]}

Van Driessche, Jozef ^{[4
]}

Stankiewicz, Pawel ^{[1
,5
]}

Lupski, James R. ^{[1
,3
,6
]}

Vermeesch, Joris R. ^{[2
]}

Cheung, Sau Wai ^{[1
]}

机构：

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

[2] Univ Ziekenhuizen Leuven, Ctr Human Genet, Louvain, Belgium

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

[4] VZW Martine Van Camp, Diest, Belgium

[5] Inst Mother & Child Hlth, Dept Med Genet, Warsaw, Poland

[6] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2010年 / 18卷 / 02期

关键词：

array comparative genomic hybridization; Sotos syndrome; microcephaly; microduplication; genomic disorders; MICRODELETION SYNDROME; MENTAL-RETARDATION; NSD1; MICRODUPLICATION; MECHANISM; PROTEIN;

D O I：

10.1038/ejhg.2009.164

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genomic rearrangements are an increasingly recognized mechanism of human phenotypic variation and susceptibility to disease. Sotos syndrome is characterized by overgrowth, macrocephaly, developmental delay and advanced osseous maturation. Haploinsufficiency of NSD1, caused by inactivating point mutations or deletion copy number variants, is the only known cause of Sotos syndrome. A recurrent 2 Mb deletion has been described with variable frequency in different populations. In this study, we report two individuals of different ethnic and geographical backgrounds, with duplications reciprocal to the common Sotos syndrome deletion. Our findings provide evidence for the existence of a novel syndrome of short stature, microcephaly, delayed bone development, speech delay and mild or absent facial dysmorphism. The phenotype is remarkably opposite to that of Sotos syndrome, suggesting a role for NSD1 in the regulation of somatic growth in humans. European Journal of Human Genetics (2010) 18, 258-261; doi: 10.1038/ejhg.2009.164; published online 21 October 2009

引用

页码：258 / 261

页数：4

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