L1 syndrome, a complex X-linked
neurological disorder, is caused by mutations in the
L1 cell adhesion molecule (
L1CAM) gene.
L1CAM molecule is a member of
immunoglobulin (Ig) superfamily of
neural cell adhesion molecules (CAMs), which plays a pivotal role in the developing nervous system. In this study, a
L1CAM gene exonic missense variant (c.1108G > A, p.G370R) was identified in two induced fetuses (abnormal fetuses), who presented
corpus callosum agenesis accompanied with
hydrocephalus. Clinical data, published literature, online database, and bioinformatic analysis suggest that the single-
nucleotide variant of
L1CAM gene is a likely pathogenic mutation. In vitro assays were performed to evaluate the effects of this variant. Based on NSC-34/COS-7 cells transfected with wild-type (L1-WT) and mutated (L1-G370R) plasmids, the
L1CAM gene exonic missense variant (c.1108G > A, p.G370R) reduced cell surface expression, induced partial endoplasmic reticulum retention, affected posttranslational modification, and reduced
protein's homophilic adhesive ability, but did not induce endoplasmic reticulum stress, which might probably associate with
L1 syndrome. Finally, 35 isolated fetuses were screened for
L1CAM gene variants by Sanger sequencing. These cases all prenatally suspected of
corpus callosum agenesis accompanied with
hydrocephalus, which may relate to
L1 syndrome. Consequently, one
L1CAM gene single missense variant (c.550C > T, p.R184W) was detected in one fetus. Our results provided evidence that the
L1CAM gene missense variant (c.1108G > A, p.G370R) may relate to
L1 syndrome. The findings of this study suggest a potential possibility of
L1CAM gene screening for prenatal diagnoses for fetuses presented
corpus callosum agenesis accompanied with
hydrocephalus.