SHOX encodes a transcription factor involved in cell-cycle and growth regulation. Here, we report the association between microduplications at the SHOX locus and autism spectrum disorders (ASD) and related neurodevelopmental conditions (NDD). The study was triggered by observations in a discovery series of 90 ASD cases, who underwent clinical genetic testing by array-comparative genomic hybridisation. A link between SHOX microduplications and ASD/NDD was subsequently supported by examination of a follow-up sample of 18,857 ASD/NDD cases, compared with 12,594 controls. Our findings suggest that SHOX microduplications are a low penetrance risk factor for ASD/NDD, with increased risk in both sexes. However, concomitant duplication of SHOX enhancers may be required to trigger NDD in females. Since specific SHOX isoforms are exclusively expressed in the developing foetal brain, this may reflect the pathogenic effect of altered SHOX protein dosage on neurodevelopment. (By Dr. Maria Tropeano, http://jmg.bmj.com/content/early/2016/04/12/jmedgenet-2015-103621 )
Dr. Maria Tropeano