Fukutin Explained

Fukutin is a eukaryotic protein necessary for the maintenance of muscle integrity, cortical histogenesis, and normal ocular development. Mutations in the fukutin gene have been shown to result in Fukuyama congenital muscular dystrophy (FCMD) characterised by brain malformation - one of the most common autosomal-recessive disorders in Japan.^[1] In humans this protein is encoded by the FCMD gene (also named FKTN), located on chromosome 9q31.^{[2] [3]} Human fukutin exhibits a length of 461 amino acids and a predicted molecular mass of 53.7 kDa.

Function

Although its function is mostly unknown, fukutin is a putative transmembrane protein that is ubiquitously expressed, although at higher levels in skeletal muscle, heart and brain.^[4] It is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of α-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development.^[3] Fukutin is expressed in the mammalian retina and is located in the Golgi complex of retinal neurons.^[5]

Clinical significance

Defects in this gene are a cause of Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X).^{[3] [6]}

See also

• Fukutin-related protein

Further reading

• Matsumoto H, Noguchi S, Sugie K . Subcellular localization of fukutin and fukutin-related protein in muscle cells. . J. Biochem. . 135 . 6 . 709–12 . 2004 . 15213246 . 10.1093/jb/mvh086 . etal.
• Puckett RL, Moore SA, Winder TL . Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation. . Neuromuscul. Disord. . 19 . 5 . 352–6 . 2009 . 19342235 . 10.1016/j.nmd.2009.03.001 . 2698593 . etal.
• Chung W, Winder TL, LeDuc CA . Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families. . Prenat. Diagn. . 29 . 6 . 560–9 . 2009 . 19266496 . 10.1002/pd.2238 . 2735827 . etal.
• Percival JM, Froehner SC . Golgi complex organization in skeletal muscle: a role for Golgi-mediated glycosylation in muscular dystrophies? . Traffic . 8 . 3 . 184–94 . 2007 . 17319799 . 10.1111/j.1600-0854.2006.00523.x . 20568065 .
• Toda T . [Fukutin, a novel protein product responsible for Fukuyama-type congenital muscular dystrophy] . Seikagaku . 71 . 1 . 55–61 . 1999 . 10067123 .
• Toda T, Kobayashi K, Kondo-Iida E . The Fukuyama congenital muscular dystrophy story. . Neuromuscul. Disord. . 10 . 3 . 153–9 . 2000 . 10734260 . 10.1016/S0960-8966(99)00109-1 . 20382548 . etal.
• Kimura K, Wakamatsu A, Suzuki Y . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 . etal.
• Cotarelo RP, Valero MC, Prados B . Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome. . Clin. Genet. . 73 . 2 . 139–45 . 2008 . 18177472 . 10.1111/j.1399-0004.2007.00936.x . etal. 10261/81951 . 21991461 . free .
• Vuillaumier-Barrot S, Quijano-Roy S, Bouchet-Seraphin C . Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype. . Neuromuscul. Disord. . 19 . 3 . 182–8 . 2009 . 19179078 . 10.1016/j.nmd.2008.12.005 . 207264089 . etal.
• Yamamoto T, Kawaguchi M, Sakayori N . Intracellular binding of fukutin and alpha-dystroglycan: relation to glycosylation of alpha-dystroglycan. . Neurosci. Res. . 56 . 4 . 391–9 . 2006 . 17005282 . 10.1016/j.neures.2006.08.009 . 53172961 . etal.
• Yoshioka M . Phenotypic spectrum of Fukutinopathy: most severe phenotype of Fukutinopathy. . Brain Dev. . 31 . 6 . 419–22 . 2009 . 18834683 . 10.1016/j.braindev.2008.07.012 . 6864803 .
• Manzini MC, Gleason D, Chang BS . Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East. . Hum. Mutat. . 29 . 11 . E231–41 . 2008 . 18752264 . 10.1002/humu.20844 . 2577713 . etal.
• Perry JR, Stolk L, Franceschini N . Meta-analysis of genome-wide association data identifies two loci influencing age at menarche. . Nat. Genet. . 41. 6. 648–650 . 2009 . 19448620 . 2942986 . 10.1038/ng.386 . etal.
• Godfrey C, Escolar D, Brockington M . Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. . Ann. Neurol. . 60 . 5 . 603–10 . 2006 . 17044012 . 10.1002/ana.21006 . 36402012 . etal.
• Godfrey C, Clement E, Mein R . Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. . Brain . 130 . Pt 10 . 2725–35 . 2007 . 17878207 . 10.1093/brain/awm212 . etal. free .
• Saredi S, Ruggieri A, Mottarelli E . Fukutin gene mutations in an Italian patient with early onset muscular dystrophy but no central nervous system involvement. . Muscle Nerve . 39 . 6 . 845–8 . 2009 . 19396839 . 10.1002/mus.21271 . 32373751 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Mercuri E, Messina S, Bruno C . Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study. . Neurology . 72 . 21 . 1802–9 . 2009 . 19299310 . 10.1212/01.wnl.0000346518.68110.60 . 9429271 . etal.
• Arimura T, Hayashi YK, Murakami T . Mutational analysis of fukutin gene in dilated cardiomyopathy and hypertrophic cardiomyopathy. . Circ. J. . 73 . 1 . 158–61 . 2009 . 19015585 . 10.1253/circj.CJ-08-0722 . etal. free .

External links

• GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview
• LOVD mutation database: FKTN

Notes and References

1. 10.1093/hmg/ddg153 . Kobayashi K, Shimizu T, Arai K, Nakamura Y, Fukui T, Toda T, Matsumura K, Imamura M, Takeda S, Kondo M, Sasaki J, Kurahashi H, Kano H, Misaki K, Tachikawa M, Murakami T, Sunada Y, Fujikado T, Terashima T . Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development . Hum. Mol. Genet. . 12 . 12 . 1449–1459 . 2003 . 12783852. free .
2. Toda T, Segawa M, Nomura Y, Nonaka I, Masuda K, Ishihara T, Sakai M, Tomita I, Origuchi Y, Suzuki M . Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33 . Nat. Genet. . 5 . 3 . 283–6 . November 1993 . 8275093 . 10.1038/ng1193-283 . 21435748 .
3. Web site: Entrez Gene: fukutin.
4. Hayashi YK, Ogawa M, Tagawa K, Noguchi S, Ishihara T, Nonaka I, Arahata K . Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy . Neurology . 57 . 1 . 115–21 . July 2001 . 11445638 . 10.1212/wnl.57.1.115. 86733816 .
5. Haro, C., Uribe, M.L., Quereda, C., Cruces, J. and Martín-Nieto, J. (2018) Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes. Molecular Vision 24, 43-58.
6. Murakami T, Hayashi YK, Noguchi S . Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness . Ann. Neurol. . 60 . 5 . 597–602 . November 2006 . 17036286 . 10.1002/ana.20973. etal. 10.1.1.515.1578 .