title: A rapid diagnostic method for a retrotransposal insertional mutation into the FCMD gene in Japanese patients with Fukuyama congenital muscular dystrophy.
abstract: Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by congenital muscular dystrophy in combination with central nervous system (CNS) abnormalities. Differential diagnosis of FCMD from Duchenne and Becker muscular dystrophies (DMD/BMD) or other types of congenital muscular dystrophy is occasionally difficult, because of their phenotypic similarity. The gene (FCMD) responsible for FCMD at 9q31 was isolated in 1998. In Japan, most FCMD-bearing chromosomes (87%) have a 3-kb retrotransposal insertion into the 3'-untranslated region (UTR) of the gene that could be derived from a single ancestral founder. Nine non-founder mutations have been identified in Japanese FCMD patients. Severe phenotype was significantly more frequent in patients who were compound heterozygotes for a point mutation and the founder mutation, than in homozygotes for the founder mutation. We developed a PCR-based diagnostic method for a rapid detection of the retrotransposal insertion mutation. Using this system, we screened 18 FCMD patients, and found 16 homozygotes and two heterozygotes for the insertion. We also evaluated the carrier frequency in the normal Japanese population. Six of 676 persons were recognized as a heterozygous carrier. Furthermore, we found three homozygotes for the FCMD founder mutation among 97 patients who had been said to have probable DMD/BMD without any DMD mutations. On the other hand, there were no FCMD homozygotes but four heterozygous carriers among 335 patients with DMD mutations. The diagnostic method we developed will provide a rapid and reliable diagnosis of FCMD, which can bring important information in genetic counseling, such as the accurate mode of inheritance, recurrence risk and a life expectancy.
authors.affiliation: Department of Pediatrics, National Higashi-Saitama Hospital, Saitama, Japan.
authors.forename: Rumiko
authors.initials: R
authors.lastname: Kato
authors.affiliation: Department of Neurology, National Higashi-Saitama Hospital, Saitama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawamura
authors.affiliation: Department of Orthopedics, Yamagata University School of Medicine, Yamagata, Japan.|Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Corporation, Kawaguchi, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Sugawara
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Corporation, Kawaguchi, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Corporation, Kawaguchi, Japan.|Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D005817:Genetic Counseling / Q000379:methods; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D009136:Muscular Dystrophies / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D011506:Proteins / Q000235:genetics*; D018626:Retroelements / Q000235:genetics
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D011506:Proteins; D018626:Retroelements