Identification of a novel nonsense homozygous mutation of LINS1 gene in two sisters with intellectual disability, schizophrenia, and anxiety

BACKGROUND: LINS1 encodes the lines homolog 1 protein that contains the Drosophila lines homologous domain. LINS1 mutations cause a rare recessive form of intellectual disability. So far, eight LINS1 mutations were reported in the literature. METHODS: We conducted a whole-genome sequencing analysis for a family with two sisters diagnosed with moderate intellectual disability, schizophrenia, and anxiety. RESULTS: We identified a novel homozygous nonsense mutation in the LINS1 in these two sisters. The mutation was a C-to-T substitution at the cDNA nucleotide position 274 that changed the amino acid glutamine at the codon 92 to stop codon (Gln92X). The mutation was transmitted from their unrelated parents, who were heterozygous carriers. CONCLUSIONS: We identified the first case of LINS1-associated neurodevelopmental disorder in Taiwan. Our findings suggest that besides intellectual disability, psychiatric diagnoses such as schizophrenia and anxiety disorder may also be part of clinical phenotypes of LINS1 mutations.