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Clinical Trial
. 2014;82(5):310-8.
doi: 10.1159/000367712. Epub 2014 Oct 8.

Copy number variants in short children born small for gestational age

Jan M Wit  1 , Hermine A van Duyvenvoorde, Jan B van Klinken, Janina Caliebe, Cathy A J Bosch, Julian C Lui, Antoinet C J Gijsbers, Egbert Bakker, Martijn H Breuning, Wilma Oostdijk, Monique Losekoot, Jeffrey Baron, Gerhard Binder, Michael B Ranke, Claudia A L Ruivenkamp
Affiliations
Clinical Trial

Copy number variants in short children born small for gestational age

Jan M Wit et al. Horm Res Paediatr. 2014.

Abstract

Background/aims: In addition to genome-wide association studies (GWAS), height-associated genes may be uncovered by studying individuals with extreme short or tall stature.

Methods: Genome-wide analysis for copy number variants (CNVs), using single nucleotide polymorphism (SNP) arrays, was performed in 49 index cases born small for gestational age with persistent short stature. Segregation analysis was performed, and genes in CNVs were compared with information from GWAS, gene expression in rodents' growth plates, and published information.

Results: CNVs were detected in 13 cases. In 5 children a known cause of short stature was found: UPD7, UPD14, a duplication of the SHOX enhancer region, an IGF1R deletion, and a 22q11.21 deletion. In the remaining 8 cases, potential pathogenic CNVs were detected, either de novo (n = 1), segregating (n = 2), or not segregating with short stature (n = 5). Bioinformatic analysis of the de novo and segregating CNVs suggested that HOXD4, AGPS, PDE11A, OSBPL6, PRKRA and PLEKHA3, and possibly DGKB and TNFRSF11B are potential candidate genes. A SERPINA7 or NRK defect may be associated with an X-linked form of short stature.

Conclusion: SNP arrays detected 5 known causes of short stature with prenatal onset and suggested several potential candidate genes.

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Conflict of interest statement

Conflict of interest

JMW has served on advisory boards for Tercica, Ipsen, Pfizer, Prolor, Teva and Biopartners, and has received speaker honorariums from Pfizer, Lilly, Ipsen and Ferring. The remaining authors declare no conflict of interest.

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