title: Two novel mutations in the adrenoleukodystrophy gene in two unrelated Japanese families and the long-term effect of bone marrow transplantation.
abstract: We identified two novel missense mutations in exon 1 of adrenoleukodystrophy (ALD) gene in two unrelated Japanese families. The first, G(874)C transition results in Arg(163)Pro substitution in the cytoplasmic domain of the ALD protein in adrenomyeloneuropathy family. The second, C(679)G results in Ser(98)Trp substitution in the first transmembrane loop in childhood onset cerebral ALD family. Both mutations cause the substitution of polar amino acid (arginine and serine) with non-polar amino acid (proline and tryptophan). Bone marrow transplantation (BMT) from his non-affected his younger sister was performed on a boy with childhood onset cerebral ALD who showed neurological deficit and brain MRI abnormalities. We evaluated the effect of BMT over a 6-year period in terms of neurological deficit, the level of very-long-chain fatty acids (VLCFA) in plasma and fibroblasts, and brain MRI. After BMT, patient's peripheral white blood cells were replaced by donor's XX ones carrying a normal ALD gene confirmed by in situ hybridization using satellite DNA of the centromere of X and Y chromosomes as probes and the level of VLCFA in lymphocytes was within normal limit. However, his neurological state progressively deteriorated. BMT was not beneficial to him.
authors.affiliation: Division of Neurology, Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, 889-1692, Miyazaki, Japan. ohi@post1.miyazaki-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Ohi
authors.forename: S
authors.initials: S
authors.lastname: Takechi
authors.forename: N
authors.initials: N
authors.lastname: Itokazu
authors.forename: K
authors.initials: K
authors.lastname: Shiomi
authors.forename: S
authors.initials: S
authors.lastname: Sugimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Antoku
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: S
authors.initials: S
authors.lastname: Matsukura
mesh_terms: D000326:Adrenoleukodystrophy / Q000235:genetics* / Q000628:therapy*; D019943:Amino Acid Substitution; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008967:Molecular Biology; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D018901:Peroxisomal Disorders / Q000235:genetics / Q000628:therapy; D017354:Point Mutation