title: Novel mutations in the fukutin gene in a boy with asymptomatic hyperCKemia.
abstract: Mutations in the fukutin gene were first identified in Japanese patients with classic Fukuyama congenital muscular dystrophy, a severe form of congenital muscular dystrophy associated with cobblestone lissencephaly and ocular defects. Patients of different ethnicities and with milder phenotypes, including limb girdle muscular dystrophy and cardiomyopathy without brain impairment, have also been reported. The hallmark of this disorder, regardless of the clinical outcome, is moderate-to-severe hypoglycosylation of alpha-dystroglycan in muscle sections. We describe the case of a boy harboring two novel mutations in fukutin gene and presenting a five-year history of asymptomatic hyperCKemia, without overt muscle, brain or ocular involvement. Genetic investigations, guided by the presence of moderate myopathic changes on muscle biopsy with loss of immunodetectable alpha-dystroglycan, led to a definitive diagnosis. Cardiac and echocardiographic examinations at follow-up disclosed low normal left ventricular function but no active cardiovascular symptoms. We suggest that fukutin mutations should be sought in asymptomatic hyperCKemia and subclinical heart dysfunction.
authors.affiliation: Molecular Medicine and Neuromuscular Lab, IRCCS Stella Maris, Pisa, Italy. Electronic address: chiara.fiorillo@inpe.unipi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fiorillo
authors.forename: Francesca
authors.initials: F
authors.lastname: Moro
authors.forename: Guja
authors.initials: G
authors.lastname: Astrea
authors.forename: Maria Aurora
authors.initials: MA
authors.lastname: Morales
authors.forename: Jacopo
authors.initials: J
authors.lastname: Baldacci
authors.forename: Maria
authors.initials: M
authors.lastname: Marchese
authors.forename: Sara
authors.initials: S
authors.lastname: Scapolan
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Roberta
authors.initials: R
authors.lastname: Battini
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics; D002648:Child; D054222:Cobblestone Lissencephaly / Q000150:complications / Q000235:genetics*; D003402:Creatine Kinase / Q000378:metabolism*; D004421:Dystonia / Q000150:complications / Q000235:genetics*; D049030:Dystroglycans / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D049030:Dystroglycans; D003402:Creatine Kinase
keywords: Alpha-dystroglycan; Cardiomyopathy; Fukutin gene; HyperCKemia; Mutations