title: Exome sequencing of two patients in a family with atypical X-linked leukodystrophy.
abstract: We encountered a family with two boys similarly showing brain atrophy with reduced white matter, hypoplasia of the brain stem and corpus callosum, spastic paralysis, and severe growth and mental retardation without speaking a word. The phenotype of these patients was not compatible with any known type of syndromic leukodystrophy. Presuming an X-linked disorder, we performed next-generation sequencing (NGS) of the transcripts of the entire X chromosome. A single lane of exome NGS in each patient was sufficient. Six potential mutations were found in both affected boys. Two missense mutations, including c.92T>C (p.V31A) in L1CAM, were potentially pathogenic, but this remained inconclusive. The other four could be excluded. Because the patients did not show adducted thumbs or hydrocephalus, the L1CAM change in this family can be interpreted as different scenarios. Personal genome analysis using NGS is certainly powerful, but interpretation of the data can be a substantial challenge requiring a lot of tasks.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: N
authors.initials: N
authors.lastname: Okamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Doi
authors.forename: H
authors.initials: H
authors.lastname: Saitsu
authors.forename: N
authors.initials: N
authors.lastname: Miyake
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D061085:Agenesis of Corpus Callosum; D001483:Base Sequence; D001933:Brain Stem / Q000002:abnormalities*; D005091:Exons; D005190:Family; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics; D010375:Pedigree
chemical_list: D039842:Neural Cell Adhesion Molecule L1