FKTN gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: fukutin (FKTN)
  • FKTN is important for the glycosylation (converting carbohydrates to glycoproteins) of alpha-dystroglycan (DAG1)
  • High level of expression in the brain, skeletal muscles and heart muscle
Clinical phenotype
(OMIM phenotype no.)
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (#253800)
  • Also known as Walker-Warburg syndrome (WWS)/Muscle Eye Brain Disease (MEB)/ Fukuyama type Congenital Muscular Dystrophy (FCMD)
  • Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 (#613152)
  • Muscular dystrophy-dystroglycanopathy (limb girdle), type C, 4 (#611588)
  • Defects in the glycosylation of alpha-dystroglycans cause 3 overlapping syndromes/dystroglycanopathies: WWS, MEB and FCMD
  • WWS—most severe phenotype; MEB—intermediate phenotype; FCMD—mildest phenotype
  • Phenotype severity is determined by the extent which the mutation affects DAG1 glycosylation
  • Cardiomyopathy, dilated 1X (#611615)
Inheritance
  • Autosomal recessive
Ocular features
Systemic features
  • Congenital muscular dystrophy
  • Brain anomalies (cobblestone lissencephaly, hydrocephalus, hypoplastic cerebellar vermis, macrocephaly, microcephaly or anencephaly)
  • Severe hypotonia
  • Occasional seizures
  • Intellectual disability
  • Developmental delays
  • Patients with WWS have a severely limited lifespan with significant CNS and ocular anomalies
  • Dilated cardiomyopathy with mild or absent motor weakness and normal intelligence have been reported
Key investigations
  • B-scan USS to measure axial length to document microphthalmia
  • Electrophysiology to determine visual potential
  • Measurement of intraocular pressure
  • Gonioscopy (if tolerated/EUA) or anterior segment OCT to identify angle abnormalities and any associated anterior segment dysgenesis
  • MRI brain and orbit
  • Systemic assessment with a paediatrician and other relevant specialists
  • Bloods (elevated creatinine kinase)
  • Skeletal muscle biopsy
Molecular diagnosisNext generation sequencing
  • Targeted gene panels
  • Whole genome sequencing
ManagementOcularSystemic
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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References

  1.  Willer T, Inamori KI, Venzke D, et al. The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated α-dystroglycan functional glycosylation. Elife 2014; 3: 3941
  2.  Toda T, Kobayashi K, Takeda S, et al. Fukuyama-type congenital muscular dystrophy (FCMD) and alpha-dystroglycanopathy. Congenital anomalies 2003; 43: 97–104
  3.  Kondo-Iida E, Kobayashi K, Watanabe M, et al. Novel Mutations and Genotype-Phenotype Relationships in 107 Families With Fukuyama-Type Congenital Muscular Dystrophy (FCMD). Hum Mol Genet 1999; 8: 2303–2309
  4.  Beltrán-Valero De Bernabé D, Van Bokhoven H, Van Beusekom E, et al. A homozygous nonsense mutation in the Fukutin gene causes a Walker-Warburg syndrome phenotype. J Med Genet 2003; 40: 845–848
  5.  Murakami T, Hayashi YK, Noguchi S, et al. Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol. 2006;60(5):597-602
  6.  Francisco R, Pascoal C, Marques-da-Silva D, et al. Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review. J Inherit Metab Dis. 2019;42(1):29-48

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Updated on November 30, 2020
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