Genetic linkage of Welander distal myopathy to chromosome 2p13

Welander distal myopathy (WDM) is an autosomal dominant myopathy with late‐adult onset characterized by slow progression of distal muscle weakness. The disorder is considered a model disease for hereditary distal myopathies and is almost only seen in Sweden and some parts of Finland. A genomewide screening has been performed in initially two Swedish families with 400 highly polymorphic microsatellite markers. We report here that the disease is linked to chromosome 2p13. Seven additional nonrelated families have subsequently been mapped to the same area where a maximum two‐point LOD score of 17.97 was obtained with the marker D2S2113 at 0.0 recombination fraction. The region has been restricted by recombinations and the finding of a common shared haplotype through all analyzed families. This restricts the gene locus region to 2.4 cM. These findings provide evidence for the involvement of a single locus for WDM. The WDM region overlaps with the linkage region for Miyoshi myopathy and limb‐girdle muscular dystrophy 2B. The dysferlin gene responsible for these disorders is considered a primary candidate gene for WDM.

[1]  J. Beckmann,et al.  A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B , 1998, Nature Genetics.

[2]  Pieter J. de Jong,et al.  Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy , 1998, Nature Genetics.

[3]  L. Edström,et al.  Welander hereditary distal myopathy, a molecular genetic comparison to hereditary myopathies with inclusion bodies , 1998, Neuromuscular Disorders.

[4]  P. D. de Jong,et al.  Generation of a 3-Mb PAC contig spanning the Miyoshi myopathy/limb-girdle muscular dystrophy (MM/LGMD2B) locus on chromosome 2p13. , 1998, Genomics.

[5]  L. Peltonen,et al.  Assignment of the tibial muscular dystrophy locus to chromosome 2q31. , 1998, American journal of human genetics.

[6]  D. Le Paslier,et al.  Genetic fine mapping of the Miyoshi myopathy locus and exclusion of eight candidate genes , 1998, Neurogenetics.

[7]  A. Lengeling,et al.  Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases. , 1997, Genomics.

[8]  S. Tsuji,et al.  Refined genetic location of the chromosome 2p-linked progressive muscular dystrophy gene. , 1997, Genomics.

[9]  L. Edström,et al.  Welander distal myopathy is not linked to other defined distal myopathy gene loci , 1997, Neuromuscular Disorders.

[10]  S. Tsuji,et al.  Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9 , 1997, Annals of neurology.

[11]  S. Tsuji,et al.  Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy. , 1996, Brain : a journal of neurology.

[12]  C. Greenberg,et al.  Limb-girdle muscular dystrophy and Miyoshi myopathy in an aboriginal Canadian kindred map to LGMD2B and segregate with the same haplotype. , 1996, American journal of human genetics.

[13]  J. Weissenbach,et al.  Genetic and physical mapping at the limb-girdle muscular dystrophy locus (LGMD2B) on chromosome 2p. , 1996, Genomics.

[14]  A. Lengeling,et al.  YAC contigs of the Rab1 and wobbler (wr) spinal muscular atrophy gene region on proximal mouse chromosome 11 and of the homologous region on human chromosome 2p. , 1996, Genomics.

[15]  Cécile Fizames,et al.  A comprehensive genetic map of the human genome based on 5,264 microsatellites , 1996, Nature.

[16]  E. Holzbaur,et al.  Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization. , 1996, Genomics.

[17]  J. Seidman,et al.  Hereditary inclusion body myopathy maps to chromosome 9p1-q1. , 1996, Human molecular genetics.

[18]  M. Passos-Bueno,et al.  Confirmation of the 2p locus for the mild autosomal recessive limb-girdle muscular dystrophy gene (LGMD2B) in three families allows refinement of the candidate region. , 1995, Genomics.

[19]  J. Haines,et al.  Linkage of Miyoshi myopathy (distal autosomal recessive muscular dystrophy) locus to chromosome 2p12-14 , 1995, Neurology.

[20]  S. Mudri,et al.  Physical mapping of the human glutamine:fructose-6-phosphate amidotransferase gene (GFPT) to chromosome 2p13. , 1995, Genomics.

[21]  F. Mastaglia,et al.  Autosomal dominant distal myopathy: linkage to chromosome 14. , 1995, American journal of human genetics.

[22]  Jurg Ott,et al.  Handbook of Human Genetic Linkage , 1994 .

[23]  K. Bushby,et al.  A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p. , 1994, Human molecular genetics.

[24]  P. Pontarotti,et al.  Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE) , 1994, American journal of human genetics.

[25]  M. Meisler,et al.  Conserved linkage of early growth response 4, annexin 4, and transforming growth factor alpha on mouse chromosome 6. , 1994, Genomics.

[26]  R. Albin,et al.  mnd2: a new mouse model of inherited motor neuron disease. , 1993, Genomics.

[27]  S. Crosby,et al.  Neural-specific expression, genomic structure, and chromosomal localization of the gene encoding the zinc-finger transcription factor NGFI-C. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Borg,et al.  Welander's distal myopathy: clinical, neurophysiological and muscle biopsy observations in young and middle aged adults with early symptoms. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[29]  J. Borg,et al.  Neurogenic involvement in distal myopathy (Welander) Histochemical and morphological observations on muscle and nerve biopsies , 1989, Journal of the Neurological Sciences.

[30]  J. Weber,et al.  Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. , 1989, American journal of human genetics.

[31]  H. Kawai,et al.  Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy. Seventeen cases in eight families including an autopsied case. , 1986, Brain : a journal of neurology.

[32]  T. Shows,et al.  The gene for human transforming growth factor α is on the short arm of chromosome 2 , 1986 .

[33]  G. Lathrop,et al.  Easy calculations of lod scores and genetic risks on small computers. , 1984, American journal of human genetics.

[34]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[35]  L. Edström.  Histochemical and histopathological changes in skeletal muscle in late-onset hereditary distal myopathy (Welander) , 1975, Journal of the Neurological Sciences.

[36]  A. Lips.  The excretion of inorganic phosphorus in children after the administration of glucose. , 2009, Acta medica Scandinavica.