2. Academic Validation
  3. Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia

Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia

  • J Hum Genet. 2006;51(8):706-710. doi: 10.1007/s10038-006-0015-3.
Yuichiro Hirose 1,  Eiji Nakashima 1,  Hirofumi Ohashi 2,  Hiroshi Mochizuki 3,  Yuki Bando 4,  Tsutomu Ogata 5,  Masanori Adachi 6,  Emi Toba 7,  Gen Nishimura 8,  Shiro Ikegawa 9
Affiliations

Affiliations

  • 1 Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
  • 2 Division of Medical Genetics, Saitama Children's Medical Center, Iwatsuki, Japan.
  • 3 Division of Endocrinology and Metabolism, Saitama Children's Medical Center, Iwatsuki, Japan.
  • 4 Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
  • 5 Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan.
  • 6 Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
  • 7 Department of Pediatrics, Tokyo Metropolitan Hachioji Children's Hospital, Hachioji, Japan.
  • 8 Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose, Japan.
  • 9 Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. [email protected].
PMID: 16832578 DOI: 10.1007/s10038-006-0015-3
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.

Figures