PMC:4574214 / 1803-3552 JSONTXT

{"project":"2_test","denotations":[{"id":"26376624-25282103-10040314","span":{"begin":645,"end":646},"obj":"25282103"},{"id":"26376624-9140395-10040315","span":{"begin":870,"end":871},"obj":"9140395"},{"id":"26376624-9590292-10040316","span":{"begin":898,"end":899},"obj":"9590292"},{"id":"26376624-22118881-10040317","span":{"begin":1116,"end":1117},"obj":"22118881"}],"text":"Background\nHuman height is a quantitative trait that follows a Gaussian distribution. Short stature is typically defined as a height more than 2 standard deviations (SD) below the corresponding mean height for a given age, gender and ethnic population. Individuals with short stature include those at the tail of the normal distribution (not necessary associated with any disorders) as well as individuals with rare disorders that restrict growth. Genome-wide association studies (GWAS) have identified over 400 independent loci associated with height in the general population which collectively explain ~20 % of the variation in adult height [1]. Rare variants with larger effects have been found in a number of genes leading to syndromic short stature disorders. For example, the SHOX gene was identified as the gene responsible for short stature in Turner syndrome [2] and Leri-Weill syndrome [3]. Recently, we demonstrated a significant association between low-frequent copy number deletions and short stature, supporting the hypothesis that rare haploinsufficient genes play significant roles in human growth [4]. We further demonstrated that an increased burden of rare deletions may also contribute to short stature in a non-clinically ascertained population, underscoring the concept that milder defects in genes known to cause syndromic short stature may contribute to short stature in the general population.\nIn this study, we focus on a recurrent CNV detected in patients with short stature. We propose that the ARID1B gene, which is the only gene intercepted by three CNVs, is a novel short stature gene. We provide additional evidence supporting that ARID1B mutations are associated with both syndromic and non-syndromic short stature."}