A Novel Missense Substitution in NSUN2 and a Stop Codon in ASPM Causes Neurological Disorders in Pakistani Families

During this study, two consanguineous Pakistani families with symptoms of intellectual disability and primary microcephaly were investigated. Affected individuals were born to phenotypically normal parents. Clinical information, including age, sex, age at walking, short stature, microcephaly, behavioral severity, intellectual disability, facial dysmorphism, muscular hypertonia, and the existence of any other illnesses, such as speech delay and epilepsy, was documented. To identify disease-causing variants, whole exome sequencing and subsequent Sanger sequencing were performed. As a result, in one of the families, a novel homozygous missense substitution in the NSUN2 gene and a stop codon in the ASPM gene in the other family were identified. Sequence analysis confirmed a homozygous pathogenic variant (c.1853G>T, p.Arg618Ile) in NSUN2 (NM_017755.6) and a stop codon (c.3978G>A, p.Tryp1326X) in ASPM (NM_018136.5). Our results broadened the mutational spectrum of both genes (NSUN2 and ASPM) causing neurological disorders in the affected individuals of Pakistani families.