Mutations In Fukutin Gene Research Articles

Fukutin gene mutations that cause left ventricular noncompaction

Fukutin gene mutations that cause left ventricular noncompaction

Homozygote Deletion of Fukutin Gene (FKTN) Exon 3 Causes Dilated Cardiomyopathy and Mild Limb-Girdle Muscular Dystrophy without Brain Involvement

Background: FKTN mutations (MIM607440) cause three different forms of muscular dystrophy-dystroglycanopathy: a severe congenital form with brain and eye anomalies (MIM253800; Fukuyama congenital muscular dystrophy = FCMD); a less severe congenital form without intellectual disability (MIM613152); and a milder limb-girdle form (MIM611588). In addition, FKTN mutations can also cause dilated cardiomyopathy (CMD1X; MIM611615) with or without limb-girdle muscle involvement.

A new mutation of the fukutin gene causing late-onset limb girdle muscular dystrophy

Defects in glycosylations of α-dystroglycan are associated with mutations in several genes, including the fukutin gene (FKTN). Hypoglycosylation of α-dystroglycan results in several forms of muscular dystrophy with variable phenotype. Outside Japan, the prevalence of muscular dystrophies related to aberrations of FKTN is rare, with only eight reported cases of limb girdle phenotype (LGMD2M). We describe the mildest affected patient outside Japan with genetically confirmed LGMD2M and onset of symptoms at age 14. She was brought to medical attention at age 12, not because of muscle weakness, but due to episodes of tachycardia caused by Wolff-Parkinson-White syndrome. On examination, she had rigid spine syndrome, a typical limb girdle dystrophy pattern of muscle weakness, cardiomyopathy, and serum CK levels >2000 IU/L (normal <150 IU/L). A homozygous, novel c.917A>G; p.Y306C mutation in the FKTN gene was found. The case confirms FKTN mutations as a cause of LGMD2M without mental retardation and expands the phenotypic spectrum for LGMD2M to include cardiomyopathy and rigid spine syndrome in the mildest affected non-Japanese patient reported so far.

EM.P.2.08 Fukutin gene mutations in an Italian patient with early onset muscular dystrophy but no central nervous system involvement

EM.P.2.08 Fukutin gene mutations in an Italian patient with early onset muscular dystrophy but no central nervous system involvement

Fukutin gene mutations in an Italian patient with early onset muscular dystrophy but no central nervous system involvement

Hypoglycosylation of alpha-dystroglycan characterizes a subgroup of muscular dystrophies of variable severity, including Fukuyama congenital muscular dystrophy. We found fukutin gene mutations in a 4.5-year-old Italian patient, with reduced alpha-dystroglycan expression, dystrophic features on muscle biopsy, hypotonia since birth, mild myopathy, but no brain involvement. Mutations in the fukutin gene can be associated with much milder phenotypes than classical Fukuyama congenital muscular dystrophy, and, although rare, can occur in non-Japanese.

Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype

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.

Congenital myopathies and congenital muscular dystrophies.

Congenital myopathies and congenital myopathic dystrophies are distinct groups of inherited diseases of muscle, genetically heterogeneous, that manifest in early life or infancy. Congenital myopathic dystrophy is characterized by a dystrophic pattern, whereas no necrotic or degenerative changes are present in congenital myopathies. Much progress has been made in recent years in clarifying the classification of the congenital myopathies. This is a clinically and genetically heterogeneous group of conditions originally classified according to unique morphological changes seen in muscle. Not unlike the later-onset muscular dystrophies, the discovery of the genetic aetiology of many of the congenital myopathies has led to a revamping of how these conditions can now be diagnosed and this should enable physicians to give a more accurate prognosis to patients and their families. New mutations in the ryanodine receptor, slow tropomyosin, troponin T1, actin, and nebulin genes have been described in the last 2 years. Clinical and genetic guidelines for conditions like nemaline rod myopathy and central core disease have been suggested. The notion of minus and surplus protein myopathies has been developed. Several groups of congenital myopathic dystrophy have been identified. In the first category, without intellectual impairment or major structural brain abnormalities, half of the cases are merosin deficient due to mutations of the laminin alpha 2 chain gene. If generally the muscular phenotype is severe, mild allelic variants have been reported with early onset dystrophies and partial merosin deficiency. Among other pure congenital myopathic dystrophies unlinked to the laminin alpha 2 gene, one form has been assigned to chromosome 1q42. In the group of congenital myopathic dystrophies associated with mental retardation and structural brain abnormalities, two main entities are genetically characterized: (1) Fukuyama congenital myopathic dystrophy, affecting the Japanese population, is due to fukutin gene mutations, and (2) the muscle eye brain syndrome assigned to chromosome 1p32-34. In several cases, the gene localization remains unknown.