title: The gene copy ratios of SMN1/SMN2 in Japanese carriers with type I spinal muscular atrophy.
abstract: Spinal muscular atrophy is an autosomal recessive neurodegenerative disorder with progressive weakness and atrophy of voluntary muscles. The survival motor neuron gene (SMN) is present in two highly homologous copies (SMN1 and SMN2) on chromosome 5q13. Homozygous deletion of exons 7 and 8 of SMN1 is responsible for spinal muscular atrophy. In spinal muscular atrophy patients, SMN2 partially compensates for the lack of SMN1. Previously, we reported the relatively high incidence of a large deletion including the SMN1 region in Japanese spinal muscular atrophy type I patients. In order to further establish the genetic background of Japanese spinal muscular atrophy type I patients, we investigated the SMN1/SMN2 ratio in the carriers. In normal individuals, there is one copy of each gene on the chromosome (the SMN1/SMN2 ratio was 1). Among 15 carriers (14 parents and one carrier sibling of Japanese type I spinal muscular atrophy patients with homozygous deletion of exons 7 and 8 of SMN1), we found that the SMN1/SMN2 ratio was 0.5 or 1 in 11 (73.3%) carriers. The remaining four carriers had an SMN1/SMN2 ratio of 1/3. This finding supports the idea that deletion rather than conversion is the main genetic event in type I spinal muscular atrophy. In addition, the ratio of SMN1/SMN2 among Japanese carriers, which was thought to be higher than that of the Western population, was compatible with the results obtained in Western populations. For further insight into the characteristic genetic background of spinal muscular atrophy in Japanese, determination of the gene copy number is essential.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-8655, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Diep Tran
authors.forename: T
authors.initials: T
authors.lastname: Kroepfl
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Nagura
authors.forename: H
authors.initials: H
authors.lastname: Ichiseki
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: Y
authors.initials: Y
authors.lastname: Sakakihara
mesh_terms: D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein