Accelerated Identification and Preliminary Validation of a Pathogenic Missense Variant in the L1CAM Gene in a Pregnant Woman With Sonographic Anomalies Using AlphaMissense.

ABSTRACT:

Background

Prenatal diagnosis of X-linked hydrocephalus caused by variants in the L1CAM gene is often complicated by the identification of Variants of Uncertain Significance (VUSs). This study showcases an accelerated diagnostic workflow using artificial intelligence (AI) to rapidly interpret a novel missense variant for a family with a history of the disorder.

Methods

We performed exome sequencing (ES) on a male fetus with significant sonographic brain anomalies from a 29-year-old pregnant woman. To efficiently analyze the resulting VUSs, we used the AI tool AlphaMissense to predict their pathogenicity and prioritize them for validation. The top candidate variant was then assessed via Sanger sequencing for co-segregation across eight maternal relatives. The structural impac

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12719231 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature