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.
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Acknowledgments
Eiji Nakashima, Hirofumi Ohashi, Gen Nishimura, and Shiro Ikegawa are members of the Japanese Skeletal Dysplasia Consortium, Tokyo, Japan. We thank the patients and their relatives who co-operated in this study. This work was supported by a grant-in-aid from Research on Child Health and Development (contract grant no. 17C-1).
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Yuichiro Hirose and Eiji Nakashima contributed equally to this work.
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Hirose, Y., Nakashima, E., Ohashi, H. et al. Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia. J Hum Genet 51, 706–710 (2006). https://doi.org/10.1007/s10038-006-0015-3
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DOI: https://doi.org/10.1007/s10038-006-0015-3
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