Abstract
BACKGROUND: Idiopathic short stature (ISS) refers to short stature with no evident etiologies. The custom genome-wide microarray specifically designed to cover height-related genes may be helpful to detect copy number variations (CNVs) in ISS patients, which may be missed by the general microarray. The aim of the study was to validate the applicability of the custom microarray and to analyze CNVs in Chinese ISS children. RESULTS: Sixty non-polymorphic CNVs were identified in 119 ISS patients. There were 13 small CNVs with a size below 50 kb, accounting for 21.7 % of all the CNVs (13/60). Five pathogenic or possibly pathogenic CNVs were detected in five patients, including deletions at 22q11.21, duplications at 4q11-q13.1, 4q12 and Yp11.32-p11.2. Taking only the pathogenic variants into account, the diagnostic yield was 2.5 % (3/119). The TMEM165, POLR2B and PDGFRA genes were analyzed as candidate genes. A 15 kb deletion in the RASA2 gene was of interest for further investigation. CONCLUSIONS: This study showed that the custom microarray is applicable to detect CNVs in patients with short stature. Candidate genes and CNVs detected in ISS patients may be helpful for CNV analysis of short stature, especially in East Asian population.