title: Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.
abstract: Fukuyama congenital muscular dystrophy (FCMD) is frequent in Japan, due to a founder mutation of the fukutin gene (FKTN). Outside Japan, FKTN mutations have only been reported in a few patients with a wide spectrum of phenotypes from Walker-Warburg syndrome to limb-girdle muscular dystrophy (LGMD2M). We studied four new Caucasian patients from three unrelated families. All showed raised serum CK initially isolated in one case and muscular dystrophy. Immunohistochemical studies and haplotype analysis led us to search for mutations in FKTN. Two patients (two sisters) presented with congenital muscular dystrophy, mental retardation, and posterior fossa malformation including cysts, and brain atrophy at Brain MRI. The other two patients had normal intelligence and brain MRI. Sequencing of the FKTN gene identified three previously described mutations and two novel missense mutations. Outside Japan, fukutinopathies are associated with a large spectrum of phenotypes from isolated hyperCKaemia to severe CMD, showing a clear overlap with that of FKRP.
authors.affiliation: AP-HP, Hôpital Bichat-Claude Bernard, Biochimie Métabolique et Cellulaire, 46 rue Henri Huchard, Paris 75018, France. Sandrine.vuillaumier@bch.aphp.fr
authors.forename: S
authors.initials: S
authors.lastname: Vuillaumier-Barrot
authors.forename: S
authors.initials: S
authors.lastname: Quijano-Roy
authors.forename: C
authors.initials: C
authors.lastname: Bouchet-Seraphin
authors.forename: S
authors.initials: S
authors.lastname: Maugenre
authors.forename: S
authors.initials: S
authors.lastname: Peudenier
authors.forename: P
authors.initials: P
authors.lastname: Van den Bergh
authors.forename: P
authors.initials: P
authors.lastname: Marcorelles
authors.forename: D
authors.initials: D
authors.lastname: Avila-Smirnow
authors.forename: M
authors.initials: M
authors.lastname: Chelbi
authors.forename: N B
authors.initials: NB
authors.lastname: Romero
authors.forename: R Y
authors.initials: RY
authors.lastname: Carlier
authors.forename: B
authors.initials: B
authors.lastname: Estournet
authors.forename: P
authors.initials: P
authors.lastname: Guicheney
authors.forename: N
authors.initials: N
authors.lastname: Seta
mesh_terms: D000328:Adult; D001284:Atrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D002648:Child; D003402:Creatine Kinase / Q000032:analysis / Q000097:blood; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D013577:Syndrome; D044465:White People; D055815:Young Adult
chemical_list: C113587:FKTN protein, human; D005819:Genetic Markers; D008565:Membrane Proteins; D003402:Creatine Kinase