De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature

BMC Genomics

Research Article

Lili Wang¹  Yanjie Fan¹  Yongguo Yu²  Joel Hirschhorn³  Xiaodong Huang⁴  Andrew Dauber⁵  RuEn Yao⁶  Yiping Shen⁷ 

[1] Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665, Kongjiang Road, 200092, Shanghai, China;Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665, Kongjiang Road, 200092, Shanghai, China;Division of Endocrinology and Genetic Metabolism, Department of Internal Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, 200127, Shanghai, China;Division of Endocrinology and Division of Genetics, Children’s Hospital Boston, 300 Longwood Ave, 02115, Boston, MA, USA;Program in Medical and Population Genetics, Metabolism Program, Broad Institute, 02141, Cambridge, MA, USA;Center for Basic and Translational Obesity Research, Children’s Hospital Boston, 02115, Boston, MA, USA;Division of Endocrinology and Genetic Metabolism, Department of Internal Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, 200127, Shanghai, China;Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, 45229, Cincinnati, OH, USA;Medical Genetics Department, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, 200127, Shanghai, China;Medical Genetics Department, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, 200127, Shanghai, China;Department of Laboratory Medicine, Boston Children’s Hospital, Boston, MA, USA;Department of Pathology, Harvard Medical School, 02115, Boston, MA, USA;Claritas Genomics, 02139, Cambridge, MA, USA;

关键词: ARID1B;    Short stature;    Haploinsufficiency;    Coffin-Siris Syndrome;    Chromatin remodeling;   

DOI  :  10.1186/s12864-015-1898-1

 received in 2015-06-03, accepted in 2015-09-08,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundHuman height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form.ResultsBased on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found.ConclusionThese results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non-syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population.

【 授权许可】

CC BY   
© Yu et al. 2015