Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia.
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.
Hirose
Yuichiro
Y
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Nakashima
Eiji
E
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Ohashi
Hirofumi
H
Division of Medical Genetics, Saitama Children's Medical Center, Iwatsuki, Japan.
Mochizuki
Hiroshi
H
Division of Endocrinology and Metabolism, Saitama Children's Medical Center, Iwatsuki, Japan.
Bando
Yuki
Y
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
Ogata
Tsutomu
T
Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan.
Adachi
Masanori
M
Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
Toba
Emi
E
Department of Pediatrics, Tokyo Metropolitan Hachioji Children's Hospital, Hachioji, Japan.
Nishimura
Gen
G
Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose, Japan.
Ikegawa
Shiro
S
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.
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
D004722:Endoribonucleases; C058330:mitochondrial RNA-processing endoribonuclease