PMC:4574214 / 17578-19553 JSONTXT

{"project":"2_test","denotations":[{"id":"26376624-25086666-10040328","span":{"begin":1069,"end":1071},"obj":"25086666"}],"text":"ARID1B and non-syndromic short stature\nWe identified four novel missense variants among 48 individuals with idiopathic short stature not associated with developmental delay. These variants were not reported in 1000 genomes project database, dbSNP database, the ESP6500 dataset or ExAC database. Functional predictions suggest deleterious effect on protein for all four variants, although two of the variants were found in family members without short stature. All four variants were absent from 1100 ethnically matched controls. We found significantly fewer deleterious novel missense variants in age, gender, and ethnicity-matched controls than in short stature patients. Importantly, two of the variants were de novo changes not detected in parents and non-affected siblings. All four patients carrying ARID1B mutation showed no signs of Coffin-Siris syndrome, or developmental or mental deficits. ARID1B de novo mutations have been shown to contribute to the heritable complex traits, such as autism spectrum disorders (ASDs), although the effect size may be small [15]. We have not established the causal relationship between these mutations and short stature, but we postulate that ARID1B is also involved with idiopathic short stature in a similar manner.\nAlmost all 70 syndromic individuals carried loss-of-function ARID1B mutations which include genic deletions (n = 27), genic duplications (n = 2), nonsense mutations (n = 14), frame shift mutations (n = 21) and a translocation (n = 1). On the other hand, all variants identified in non-syndromic short stature are missense variants. Based on this finding, we postulate that while complete loss of the ARID1B gene product causes a syndrome that involves developmental delay, intellectual disability, dysmorphism and short stature, missense mutations may cause isolated short stature without developmental defects. Further testing of more non-syndromic short stature patient is warranted to validate such hypothesis."}