Reviewed August 2013
What is the official name of the FKTN gene?
The official name of this gene is “fukutin.”
FKTN is the gene's official symbol. The FKTN gene is also known by other names, listed below.
What is the normal function of the FKTN gene?
The FKTN gene (formerly known as FCMD) provides instructions for making a protein called fukutin. This protein is present in many of the body's tissues but is particularly abundant in muscles used for movement (skeletal muscles), the heart, and the brain.
Although the exact function of fukutin is unclear, researchers predict that it may chemically modify a protein called alpha (α)-dystroglycan. Specifically, fukutin is thought to add chains of sugar molecules to α-dystroglycan through a process known as glycosylation. Glycosylation is critical for the normal function of α-dystroglycan.
The α-dystroglycan protein helps anchor the structural framework inside each cell (cytoskeleton) to the lattice of proteins and other molecules outside the cell (extracellular matrix). In skeletal muscles, glycosylated α-dystroglycan helps stabilize and protect muscle fibers. In the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.
How are changes in the FKTN gene related to health conditions?
- Fukuyama congenital muscular dystrophy - caused by mutations in the FKTN gene
Mutations in the FKTN gene cause Fukuyama congenital muscular dystrophy, a condition that causes muscle weakness and brain and eye abnormalities. This form of congenital muscular dystrophy is seen almost exclusively in Japan. Virtually everyone with this condition has at least one copy of the same mutation, an insertion of about 3,000 extra DNA building blocks (3 kilobases) in the FKTN gene. This insertion occurs in a part of the gene known as the 3' untranslated region, which helps regulate the gene's activity. Researchers believe that the three-kilobase insertion reduces the amount of fukutin protein that is produced from the gene.
A shortage of fukutin likely prevents the normal glycosylation of α-dystroglycan. As a result, α-dystroglycan can no longer effectively anchor cells to the proteins and other molecules that surround them. Without functional α-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, which affects the development, structure, and function of skeletal muscles in people with Fukuyama congenital muscular dystrophy.
Defective α-dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead appears bumpy and irregular. Less is known about the effects of FKTN mutations in other parts of the body.
- Walker-Warburg syndrome - caused by mutations in the FKTN gene
FKTN gene mutations have been identified in a small number of people with Walker-Warburg syndrome, the most severe form of congenital muscular dystrophy. This condition is found in populations worldwide. Like Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome is associated with muscle weakness and eye and brain abnormalities, including cobblestone lissencephaly; however, individuals with Walker-Warburg syndrome have more severe eye abnormalities and live only into infancy or early childhood. The FKTN gene mutations associated with this condition prevent the production of any functional fukutin protein, which leads to the severe muscle, eye, and brain problems associated with it.
- other disorders - caused by mutations in the FKTN gene
Mutations in the FKTN gene cause other disorders that affect skeletal muscles and the heart. Unlike Fukuyama congenital muscular dystrophy, which is mostly limited to the Japanese population, these conditions have been described in several populations worldwide.
Mutations in the FKTN gene have been found in a few families with a less severe form of muscular dystrophy known as limb-girdle muscular dystrophy type 2M (LGMD2M). This condition causes muscle weakness but does not affect the brain.
Several people with a heart condition called dilated cardiomyopathy have been found to have mutations in the FKTN gene. This condition weakens and enlarges the heart, preventing it from pumping blood efficiently. When dilated cardiomyopathy is associated with FKTN gene mutations, it is known as type 1X (DCM1X). In addition to heart problems, some people with DCM1X have experienced mild muscle weakness beginning in adulthood.
Changes in the FKTN gene that reduce but do not eliminate the production of fukutin lead to the somewhat less severe medical problems seen in LGMD2M and DCM1X.
Where is the FKTN gene located?
Cytogenetic Location: 9q31.2
Molecular Location on chromosome 9: base pairs 105,558,119 to 105,641,118
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/2218))
The FKTN gene is located on the long (q) arm of chromosome 9 at position 31.2.
More precisely, the FKTN gene is located from base pair 105,558,119 to base pair 105,641,118 on chromosome 9.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about FKTN?
You and your healthcare professional may find the following resources about FKTN helpful.
Educational resources - Information pages
- Molecular Cell Biology (fourth edition, 2000): Protein Glycosylation in the ER and Golgi Complex (http://www.ncbi.nlm.nih.gov/books/NBK21744/)
- Neuromuscular Disease Center, Washington University (http://neuromuscular.wustl.edu/syncm.html)
Gene Reviews - Clinical summary
- Gene Review: Congenital Muscular Dystrophy Overview (http://www.ncbi.nlm.nih.gov/books/NBK1291)
- Gene Review: Dilated Cardiomyopathy Overview (http://www.ncbi.nlm.nih.gov/books/NBK1309)
- Gene Review: Fukuyama Congenital Muscular Dystrophy (http://www.ncbi.nlm.nih.gov/books/NBK1206)
- Gene Review: Limb-Girdle Muscular Dystrophy Overview (http://www.ncbi.nlm.nih.gov/books/NBK1408)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for FKTN (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=2218%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28FKTN%5BTIAB%5D%29%20OR%20%28fukutin%5BTIAB%5D%29%20OR%20%28FCMD%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- CARDIOMYOPATHY, DILATED, 1X (http://omim.org/entry/611615)
- FUKUTIN (http://omim.org/entry/607440)
- MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4 (http://omim.org/entry/611588)
Research Resources - Tools for researchers
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=3622)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2218)
What other names do people use for the FKTN gene or gene products?
- Fukuyama type congenital muscular dystrophy protein
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding FKTN?
extracellular matrix ;
muscle cells ;
muscular dystrophy ;
neuronal migration ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Broglio L, Tentorio M, Cotelli MS, Mancuso M, Vielmi V, Gregorelli V, Padovani A, Filosto M. Limb-girdle muscular dystrophy-associated protein diseases. Neurologist. 2010 Nov;16(6):340-52. doi: 10.1097/NRL.0b013e3181d35b39. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21150381?dopt=Abstract)
- Cotarelo RP, Valero MC, Prados B, Peña A, Rodríguez L, Fano O, Marco JJ, Martínez-Frías ML, Cruces J. Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome. Clin Genet. 2008 Feb;73(2):139-45. doi: 10.1111/j.1399-0004.2007.00936.x. Epub 2007 Dec 19. (http://www.ncbi.nlm.nih.gov/pubmed/18177472?dopt=Abstract)
- de Bernabé DB, van Bokhoven H, van Beusekom E, Van den Akker W, Kant S, Dobyns WB, Cormand B, Currier S, Hamel B, Talim B, Topaloglu H, Brunner HG. A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype. J Med Genet. 2003 Nov;40(11):845-8. (http://www.ncbi.nlm.nih.gov/pubmed/14627679?dopt=Abstract)
- Godfrey C, Escolar D, Brockington M, Clement EM, Mein R, Jimenez-Mallebrera C, Torelli S, Feng L, Brown SC, Sewry CA, Rutherford M, Shapira Y, Abbs S, Muntoni F. Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. Ann Neurol. 2006 Nov;60(5):603-10. (http://www.ncbi.nlm.nih.gov/pubmed/17044012?dopt=Abstract)
- 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. 2001 Jul 10;57(1):115-21. (http://www.ncbi.nlm.nih.gov/pubmed/11445638?dopt=Abstract)
- Kobayashi K, Nakahori Y, Miyake M, Matsumura K, Kondo-Iida E, Nomura Y, Segawa M, Yoshioka M, Saito K, Osawa M, Hamano K, Sakakihara Y, Nonaka I, Nakagome Y, Kanazawa I, Nakamura Y, Tokunaga K, Toda T. An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature. 1998 Jul 23;394(6691):388-92. (http://www.ncbi.nlm.nih.gov/pubmed/9690476?dopt=Abstract)
- Kondo-Iida E, Kobayashi K, Watanabe M, Sasaki J, Kumagai T, Koide H, Saito K, Osawa M, Nakamura Y, Toda T. Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD). Hum Mol Genet. 1999 Nov;8(12):2303-9. (http://www.ncbi.nlm.nih.gov/pubmed/10545611?dopt=Abstract)
- Murakami T, Hayashi YK, Noguchi S, Ogawa M, Nonaka I, Tanabe Y, Ogino M, Takada F, Eriguchi M, Kotooka N, Campbell KP, Osawa M, Nishino I. Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol. 2006 Nov;60(5):597-602. (http://www.ncbi.nlm.nih.gov/pubmed/17036286?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2218)
- Saito K, Osawa M, Wang ZP, Ikeya K, Fukuyama Y, Kondo-Iida E, Toda T, Ohashi H, Kurosawa K, Wakai S, Kaneko K. Haplotype-phenotype correlation in Fukuyama congenital muscular dystrophy. Am J Med Genet. 2000 May 29;92(3):184-90. (http://www.ncbi.nlm.nih.gov/pubmed/10817652?dopt=Abstract)
- Saito Y, Yamamoto T, Mizuguchi M, Kobayashi M, Saito K, Ohno K, Osawa M. Altered glycosylation of alpha-dystroglycan in neurons of Fukuyama congenital muscular dystrophy brains. Brain Res. 2006 Feb 23;1075(1):223-8. Epub 2006 Feb 7. (http://www.ncbi.nlm.nih.gov/pubmed/16466646?dopt=Abstract)
- Silan F, Yoshioka M, Kobayashi K, Simsek E, Tunc M, Alper M, Cam M, Guven A, Fukuda Y, Kinoshita M, Kocabay K, Toda T. A new mutation of the fukutin gene in a non-Japanese patient. Ann Neurol. 2003 Mar;53(3):392-6. (http://www.ncbi.nlm.nih.gov/pubmed/12601708?dopt=Abstract)
- Toda T, Kobayashi K, Takeda S, Sasaki J, Kurahashi H, Kano H, Tachikawa M, Wang F, Nagai Y, Taniguchi K, Taniguchi M, Sunada Y, Terashima T, Endo T, Matsumura K. Fukuyama-type congenital muscular dystrophy (FCMD) and alpha-dystroglycanopathy. Congenit Anom (Kyoto). 2003 Jun;43(2):97-104. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12893968?dopt=Abstract)
- Yis U, Uyanik G, Heck PB, Smitka M, Nobel H, Ebinger F, Dirik E, Feng L, Kurul SH, Brocke K, Unalp A, Özer E, Cakmakci H, Sewry C, Cirak S, Muntoni F, Hehr U, Morris-Rosendahl DJ. Fukutin mutations in non-Japanese patients with congenital muscular dystrophy: less severe mutations predominate in patients with a non-Walker-Warburg phenotype. Neuromuscul Disord. 2011 Jan;21(1):20-30. doi: 10.1016/j.nmd.2010.08.007. Epub 2010 Oct 18. (http://www.ncbi.nlm.nih.gov/pubmed/20961758?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.