Relevance to Autism

A de novo frameshift variant and several de novo missense variants in the LHX2 gene have been identified in ASD probands from the Autism Sequencing Consortium and the SPARK cohort (Satterstrom et al., 2020; Zhou et al., 2022; Trost et al., 2022). Schmid et al., 2023 reported 19 individuals from 18 families, including the three ASD probands from the SPARK cohort, with LHX2 variation and presenting with a variable neurodevelopmental disorder characterized by developmental delay, autism spectrum disorder and other behavioral abnormalities, variable intellectual disability, and microcephaly; four of the LHX2 missense variants identified in affected individuals, including one that was observed in a SPARK ASD proband, were shown experimentally to result in nucleolar accumulation, impaired interaction with co-factor LDB1, and/or reduced transcriptional activation by luciferase assay.

Molecular Function

This gene encodes a protein belonging to a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein may function as a transcriptional regulator. The protein can recapitulate or rescue phenotypes in Drosophila caused by a related protein, suggesting conservation of function during evolution.

External Links

References