The Fukuyama congenital muscular dystrophy story

Fukuyama congenital muscular dystrophy is one of the most common autosomal recessive disorders in the Japanese population, characterized by congenital muscular dystrophy in combination with cortical dysgenesis (micropolygyria ). Recently, we have identified the gene responsible for fukuyama congenita l muscular dystrophy on 9q31, which encodes a novel 461-amino-acid protein termed fukutin. Most fukuyama congenital muscular dystrophy-bearing chromos omes are derived from a single ancestral founder (87%), and a 3 kb-retrotra nsposal insertion into the 3' untranslated region of this gene was found to be a founder mutation. Two independent point mutations causing premature t ermination confirmed that that this gene is responsible for Fukuyama congen ital muscular dystrophy. Fukuyama congenital muscular dystrophy is the firs t human disease to be caused by an ancient retrotransposal integration. Fuk utin contains an amino-terminal signal sequence, which together with result s from transfection experiments suggests that it is an extracellular protei n. Discovery of the fukuyama congenital muscular dystrophy gene represents an important step toward greater understanding of the pathogenesis of muscu lar dystrophies and also of normal brain development. (C) 2000 Elsevier Sci ence B.V. All rights reserved.