TY - JOUR
AU - Eri Kondo-Iida, Kazuhiro Kobayashi, Masashi Watanabe, Junko Sasaki, Toshiyuki Kumagai, Hiroyoshi Koide, Kayoko Saito, Makiko Osawa, Yusuke Nakamura, Tatsushi Toda
AB - Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in the Japanese population, is characterized by congenital muscular dystrophy in combination with cortical dysgenesis (micropolygyria). Recently, we identified, on chromosome 9q31, the gene responsible for FCMD, which encodes a novel 461 amino acid protein which we have termed fukutin. Most FCMD-bearing chromosomes examined to date (87%) have been derived from a single ancestral founder, whose mutation consisted of a 3 kb retrotransposal insertion in the 3′ non-coding region of the fukutin gene. FCMD is the first human disease known to be caused primarily by an ancient retrotransposal integration. We undertook a systematic analysis of the FCMD gene in 107 unrelated patients, and identified four novel non-founder mutations in five of them: one missense, one nonsense, one L1 insertion and a 1 bp insertion. The frequency of severe phenotypes, including Walker-Walberg syndrome-like manifestations such as hydrocephalus and microphthalmia, was significantly higher among probands who were compound heterozygotes carrying a point mutation on one allele and the founder mutation on the other, than it was among probands who were homozygous for the 3 kb retrotransposon. Remarkably, we detected no FCMD patients with non-founder (point) mutations on both alleles of the gene, and suggest that such cases might be embryonic-lethal. This could explain why few FCMD cases are reported in non-Japanese populations. Our results provided strong evidence that loss of function of fukutin is the major cause of FCMD, and appeared to shed some light on the mechanism responsible for the broad clinical spectrum seen in this disease. © 1999 Oxford University Press « Previous | Next Article » Table of Contents This Article Hum. Mol. Genet. (1999) 8 (12): 2303-2309. doi: 10.1093/hmg/8.12.2303 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Article Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Kondo-Iida, E. Articles by Toda, T. Search for related content PubMed PubMed citation Articles by Kondo-Iida, E. Articles by Kobayashi, K. Articles by Watanabe, M. Articles by Sasaki, J. Articles by Kumagai, T. Articles by Koide, H. Articles by Saito, K. Articles by Osawa, M. Articles by Nakamura, Y. Articles by Toda, T. 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TI - Novel Mutations and Genotype-Phenotype Relationships in 107 Families With Fukuyama-Type Congenital Muscular Dystrophy (FCMD)
JO - Human Molecular Genetics
DO - 10.1093/hmg/8.12.2303
DA - 1999-11-01
UR - https://www.deepdyve.com/lp/oxford-university-press/novel-mutations-and-genotype-phenotype-relationships-in-107-families-0koIXTKtH4
SP - 2303
VL - 8
IS - 12
DP - DeepDyve
ER -