Identical by descent L1CAM mutation in two apparently unrelated families with intellectual disability without L1 syndrome.

Mutations in the L1 Cell Adhesion Molecule (L1CAM) gene (MIM#308840) cause a variety of X-linked recessive neurological disorders collectively called L1 syndrome. Using massively parallel sequencing (MPS) of the X-chromosome exome, we identified a novel missense variant in L1CAM in two Caucasian families with mild-moderate intellectual disability without obvious L1 syndrome features. These families were not known to be related. SNP data extracted from MPS identified a 5.6 cM tract of identity by descent (IBD), encompassing the L1CAM gene, between the DNA of the two probands. This cannot be explained by chance alone and strongly implies that the two families are related. It also suggests that the L1CAM (NM_000425.3, c.604G > A, p.D202N) variant is pathogenic. This report also demonstrates the usefulness of additional information, which can be extracted from exome sequencing data.