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.
Robinson Research Institute, The University of Adelaide, Adelaide, SA 5000, Australia; School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5000, Australia.
Marie
M
Shaw
Discipline of Genetics, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, SA 5000, Australia.
Tzu Ying
TY
Yap
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia.
Lyndal
L
Henden
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Department of Mathematics and Statistics, University of Melbourne, Melbourne, Australia.
Melanie
M
Bahlo
Robinson Research Institute, The University of Adelaide, Adelaide, SA 5000, Australia; School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5000, Australia.
Alison
A
Gardner
Max Planck Institute for Molecular Genetics, Department Human Molecular Genetics, Ihnestrasse 73, Berlin, D-14195, Germany.
Vera M
VM
Kalscheuer
School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5000, Australia; SA Pathology, Women's and Children's Hospital, Adelaide, SA 5006, Australia.
Eric
E
Haan
GOLD NSW, Hunter Genetics, Newcastle, Australia.
Louise
L
Christie
GOLD NSW, Hunter Genetics, Newcastle, Australia.
Anna
A
Hackett
Robinson Research Institute, The University of Adelaide, Adelaide, SA 5000, Australia; School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5000, Australia. Electronic address: jozef.gecz@adelaide.edu.au.
Jozef
J
Gecz
D000328:Adult; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*
D039842:Neural Cell Adhesion Molecule L1
Identical by descent; L1CAM; Massively parallel sequencing; X-chromosome exome; X-linked intellectual disability