title: Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia.
abstract: Cartilage-hair hypoplasia (CHH), or metaphyseal dysplasia, McKusick type, is an autosomal recessive disease with diverse clinical manifestations. CHH is caused by mutations in RMRP (ribonuclease mitochondrial RNA processing), the gene encoding the RNA component of the ribonucleoprotein complex RNase MRP. A common founder mutation, 70A>G has been reported in the Finnish and Amish populations. We screened 11 Japanese patients with CHH for RMRP mutations and identified mutations in five probands, including three novel mutations (16-bp dup at +1, 168G>A, and 217C>T). All patients were compound heterozygotes for an insertion or duplication in the promoter or 5'-transcribed regions and a point mutation in the transcribed region. Two recurrent mutations were unique to the Japanese population: a 17-bp duplication at +3 and 218A>G. Haplotype analysis revealed that the two mutations common in Japanese individuals were contained within distinct haplotypes. Through this analysis, we have identified a unique mutation spectrum and founder mutations in the Japanese population.
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hirose
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakashima
authors.affiliation: Division of Medical Genetics, Saitama Children's Medical Center, Iwatsuki, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.affiliation: Division of Endocrinology and Metabolism, Saitama Children's Medical Center, Iwatsuki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Bando
authors.affiliation: Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Pediatrics, Tokyo Metropolitan Hachioji Children's Hospital, Hachioji, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Toba
authors.affiliation: Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. sikegawa@ims.u-tokyo.ac.jp.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000293:Adolescent; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002356:Cartilage / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004722:Endoribonucleases / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006197:Hair / Q000002:abnormalities*; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: D004722:Endoribonucleases; C058330:mitochondrial RNA-processing endoribonuclease