Identification of a Novel Missense Homozygous Variant in LINS1 in Two Distinct Iranian Families With Consanguineous Marriage.

backgroundLINS1, the human homolog of the Drosophila segment polarity gene, encodes a key regulator of the Wingless/Wnt signaling pathway. While numerous genes have been implicated in intellectual disability (ID), only a limited number have been conclusively associated with autosomal recessive intellectual disability (ARID). Variants in LINS1 have been identified as one such cause.

methodsIn this study, we employed exome sequencing (ES) to investigate the genetic basis of ID in two consanguineous Iranian families. This variant was confirmed by Sanger sequencing, and segregation analysis supported its pathogenicity. Additionally, in silico analyses were conducted to explore the protein-protein interaction network of LINS1 and its functional connections to ID-associated proteins.

resultsWe identified a novel homozygous missense variant in LINS1 (c.1354G>C), leading to an alanine-to-proline substitution (p.Ala452Pro) in exon six.

conclusionOur findings provide new molecular and clinical insights into the role of LINS1 in ARID, expanding the genetic landscape of ID. This discovery has significant implications for genetic counseling and prenatal diagnosis, aiding in the identification of at-risk couples.