The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases

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Abstract
Cartilage‐hair hypoplasia (CHH), or McKusick type metaphyseal chondrodysplasia, was originally described in the Old Order Amish in the United States and subsequently found to be unusually frequent among Finns. The major mutation causing CHH in Finns is a 70A → G nucleotide substitution in the RMRP gene, which encodes the untranslated RNA that is a component of mitochondrial RNA‐processing endoribonuclease. Here we report that the same mutation is the most frequent one, perhaps the only one, in the Amish population in which CHH was first characterized. The fact that the mutation segregates with the same major haplotype in these two populations and others suggests that it is very ancient. Unlike some other ordinarily rare recessive disorders that are limited in their high frequency to a single Amish deme (subisolate), e.g., Ellis‐van Creveld syndrome, CHH occurs in high frequency in at least three distinct Amish demes, indicating, along with genealogic data, that there were multiple heterozygotes among the founders, as proposed by McKusick et al. [1965: Bull Johns Hopkins Hosp 116:231–272]. Published 2003 Wiley‐Liss, Inc.
Funding Information
  • March of Dimes Birth Defects Foundation (6-FY99-586, 6-FY00-294)
  • Helsinki University's Research Funds
  • Helsinki University Central Hospital Fund
  • Intramural Research Programs of the National Human Genome Research Institute and the National Institute on Aging