Complex genomic variants contribute toward the genetic architecture of autism spectrum disorder.

Genetic factor plays a critical role in the etiology of autism spectrum disorder (ASD). Both common variants with a small effect and rare mutations with a large effect contribute toward the genetic basis of ASD, showing the high genetic heterogeneity of ASD. Genomic rearrangements account for around 10-15% of its genetic landscape. However, they are highly individualized and each of them has a very rare frequency.

Identification of a microdeletion at Xp22.13 in a Taiwanese family presenting with Nance-Horan syndrome.

Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital cataracts, dental anomalies and mental retardation. The disease has been linked to a novel gene termed NHS located at Xp22.13. The majority of pathogenic mutations of the disease include nonsense mutations and small deletions and insertions that lead to truncation of the NHS protein. In this study, we identified a microdeletion of ∼ 0.92 Mb at Xp22.13 detected by array-based comparative genomic hybridization in two brothers presenting congenital cataract, dental anomalies, facial dysmorphisms and mental retardation. The deleted region encompasses the REPS2, NHS, SCML1 and RAI2 genes, and was transmitted from their carrier mother who presented only mild cataract. Our findings are in line with several recent case reports to indicate that genomic rearrangement involving the NHS gene is an important genetic etiology underlying NHS.