title: De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature.
abstract: BACKGROUND
  Human 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.
  
  
  RESULTS
  Based 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665, Kongjiang Road, Shanghai, 200092, China. yuyongguo@shsmu.edu.cn.|Division of Endocrinology and Genetic Metabolism, Department of Internal Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. yuyongguo@shsmu.edu.cn.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Medical Genetics Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. yaoruen@126.com.
authors.forename: RuEn
authors.initials: R
authors.lastname: Yao
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665, Kongjiang Road, Shanghai, 200092, China. leafrose210@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665, Kongjiang Road, Shanghai, 200092, China. fanyanjie13@163.com.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Division of Endocrinology and Genetic Metabolism, Department of Internal Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. jcperkesh@126.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Division of Endocrinology and Division of Genetics, Children's Hospital Boston, 300 Longwood Ave, Boston, MA, 02115, USA. joelh@broadinstitute.org.|Program in Medical and Population Genetics, Metabolism Program, Broad Institute, Cambridge, MA, 02141, USA. joelh@broadinstitute.org.|Center for Basic and Translational Obesity Research, Children's Hospital Boston, Boston, MA, 02115, USA. joelh@broadinstitute.org.
authors.forename: Joel
authors.initials: J
authors.lastname: Hirschhorn
authors.affiliation: Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. Andrew.Dauber@cchmc.org.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dauber
authors.affiliation: Medical Genetics Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. yiping.shen@childrens.harvard.edu.|Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA. yiping.shen@childrens.harvard.edu.|Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA. yiping.shen@childrens.harvard.edu.|Claritas Genomics, Cambridge, MA, 02139, USA. yiping.shen@childrens.harvard.edu.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000015:Abnormalities, Multiple; D000293:Adolescent; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics; D004392:Dwarfism / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005260:Female; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006228:Hand Deformities, Congenital; D006801:Humans; D008607:Intellectual Disability; D008297:Male; D008844:Micrognathism; D009154:Mutation; D009333:Neck / Q000002:abnormalities; D012189:Retrospective Studies; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C497837:ARID1B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors