ausblenden:
Schlagwörter:
Adult
Female
Genetic Diseases, X-Linked/diagnosis/*genetics
Humans
Intellectual Disability/diagnosis/*genetics
Male
*Mutation, Missense
Neural Cell Adhesion Molecule L1/*genetics
Pedigree
Polymorphism, Single Nucleotide
Spastic Paraplegia, Hereditary/diagnosis/*genetics
Identical by descent
L1cam
Massively parallel sequencing
X-chromosome exome
X-linked intellectual disability
Zusammenfassung:
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.
