Human Molecular Genetics, Vol 8, 2303-2309, Copyright © 1999 by Oxford University Press
E Kondo-Iida, K Kobayashi, M Watanabe, J Sasaki, T Kumagai, H Koide, K Saito, M Osawa, Y Nakamura and T Toda
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 under-took 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.
ARTICLES
Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD)
Laboratory of Genome Medicine and
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Kanagawa, A. Nishimoto, T. Chiyonobu, S. Takeda, Y. Miyagoe-Suzuki, F. Wang, N. Fujikake, M. Taniguchi, Z. Lu, M. Tachikawa, et al. Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy Hum. Mol. Genet., February 15, 2009; 18(4): 621 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakanishi, M. Sakauchi, Y. Kaneda, H. Tomimatsu, K. Saito, M. Nakazawa, and M. Osawa Cardiac Involvement in Fukuyama-type Congenital Muscular Dystrophy Pediatrics, June 1, 2006; 117(6): e1187 - e1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Barkovich, R. I. Kuzniecky, G. D. Jackson, R. Guerrini, and W. B. Dobyns A developmental and genetic classification for malformations of cortical development Neurology, December 27, 2005; 65(12): 1873 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Penzkofer, T. Dandekar, and T. Zemojtel L1Base: from functional annotation to prediction of active LINE-1 elements Nucleic Acids Res., January 1, 2005; 33(suppl_1): D498 - D500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Beltran-Valero de Bernabe, H van Bokhoven, E van Beusekom, W Van den Akker, S Kant, W B Dobyns, B Cormand, S Currier, B Hamel, B Talim, et al. A homozygous nonsense mutation in the Fukutin gene causes a Walker-Warburg syndrome phenotype J. Med. Genet., November 1, 2003; 40(11): 845 - 848. [Full Text] [PDF]
|
|
|
|
|
|
S. Takeda, M. Kondo, J. Sasaki, H. Kurahashi, H. Kano, K. Arai, K. Misaki, T. Fukui, K. Kobayashi, M. Tachikawa, et al. Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development Hum. Mol. Genet., June 15, 2003; 12(12): 1449 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Taniguchi, K. Kobayashi, K. Saito, H. Yamanouchi, A. Ohnuma, Y. K. Hayashi, H. Manya, D. K. Jin, M. Lee, E. Parano, et al. Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease Hum. Mol. Genet., March 1, 2003; 12(5): 527 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Esapa, M. A. Benson, J. E. Schroder, E. Martin-Rendon, M. Brockington, S. C. Brown, F. Muntoni, S. Kroger, and D. J. Blake Functional requirements for fukutin-related protein in the Golgi apparatus Hum. Mol. Genet., December 15, 2002; 11(26): 3319 - 3331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sasaki, K. Ishikawa, K. Kobayashi, E. Kondo-Iida, M. Fukayama, H. Mizusawa, S. Takashima, Y. Sakakihara, Y. Nakamura, and T. Toda Neuronal expression of the fukutin gene Hum. Mol. Genet., December 1, 2000; 9(20): 3083 - 3090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Goodier, E. M. Ostertag, and H. H. Kazazian Jr Transduction of 3'-flanking sequences is common in L1 retrotransposition Hum. Mol. Genet., March 1, 2000; 9(4): 653 - 657. [Abstract] [Full Text] [PDF]
|
|