[Fukuyama-type congenital muscular dystrophy].

Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by congenital muscular dystrophy in combination with cortical dysgenesis and ocular abnormality. We identified on chromosome 9 q31 the gene for FCMD, which encodes a novel 461-amino-acid protein (fukutin). Most FCMD-bearing chromosomes 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. Some point mutations causing premature termination were found. Amino acid sequence and transfection experiments suggest that fukutin may be an extracellular protein. Pathological study on the brain of the FCMD fetuses revealed that the glia-limitans and basement-membrane complex had frequent breaks. Because of this, developing neurons were shown to overmigrate in the cerebrum. Electron microscopy of the skeletal muscle in FCMD showed that the basal lamina has a disrupted appearance. Thus, a structural alteration of the basal lamina appears to play a key role in the pathophysiology of FCMD. The spectrum of clinical variability of FCMD is much wider than recognized previously. Point mutations have been seen to render the FCMD phenotype rather severe. FCMD could give rise to only in the Japanese who have a milder retrotransposon mutation.