Single nucleotide polymorphism array analysis of 102 patients with developmental delay and/or intellectual disability from Fujian, China

Abstract

Developmental delay/intellectual disability (DD/ID) is a complex and phenotypically heterogeneous neurodevelopmental disorder characterized by significant deficits in cognitive and adaptive skills, debuting during the developmental period. In this study, we evaluated the usefulness of single nucleotide polymorphism (SNP) array in the detection of genetic causes of 102 DD/ID patients from Fujian (China). Of them, clinically relevant variants (including pathogenic and likely pathogenic), variants of uncertain significance (VOUS), and no clinically relevant variants (including likely benign and benign) were detected in 19, 4 and 79 patients, accounting for 18.6%, 3.9% and 77.5%, respectively, with a diagnostic yield of 18.6% in our study. Furthermore, we divided 19 clinically relevant variants into 4 groups, including chromosome aneuploidy (n = 1); large copy number variants (CNVs) (>10 Mb) (n = 8); known genomic disorders (n = 8), and likely pathogenic CNVs (n = 2). Moreover, we discussed our findings with respect to 4 cases of VOUS. Overall, we confirmed that DD/ID is a genetically heterogeneous condition and emphasized the importance of using genome-wide SNP array in the detection of its genetic causes. Additionally, we provided clinical and molecular data of patients with causal chromosomal aberrations, and discussed the potential implication in DD/ID of genes located within those CNVs or regions of homozygosity.

Keywords: Copy number variant; Developmental delay; Intellectual disability; Region of homozygosity; Single nucleotide polymorphism array.