A novel de novo heterozygous deletion at 13q14.2-q21.1 in two siblings with mild intellectual disability

Intellectual disability (ID) is characterized by limited intellectual functioning and adaptive behavior, with a global prevalence of ~1-2%. Around 50% of ID cases have a genetic basis, with chromosomal and single gene mutations accounting for ~17-19% and rare de novo copy number variations (CNVs) for ~15% of the total cases. Thus, ~30-50% of the cases still remain unexplained. We investigated a north-eastern Indian family with two male children affected with mild syndromic ID. Both the affected siblings were first screened for mutations in genes implicated with syndromic ID on clinical suspicion (NHS and OCRL) in this family and found to be negative. Further, CNV analysis was carried out in the family using HumanCytoSNP-12 oligonucleotide array. Analysis revealed a 9.8 Mb de novo heterozygous deletion at 13q14.2-q21.1 that was shared among the affected siblings but not with their unaffected brother and parents. The deletion was confirmed by using quantitative-PCR which revealed a significant loss in copy number in both the affected siblings. This region encompasses genes functionally relevant to the ID phenotype, such as CKAP2, SUGT1, LECT1, DCLK1and SMAD9. A range of deletions spanning 13q13.3-13qter with variable phenotypes and haploinsufficiency have been reported in literature, but a de novo heterozygous deletion shared among siblings as seen in this study is very rare. Though the mechanism underlying this deletion remains unknown, our finding reiterates the notable contribution of this chromosomal region to ID, warranting more such studies to identify genetic underpinnings underlying ID. Such discoveries would lead to more personalized treatment regimens for ID individuals.