Clinical and genetic characteristics and diagnostic features of Landouzy–Dejerine facioscapulohumeral muscular dystrophy

Abstract

Landouzy–Dejerine facioscapulohumeral muscular dystrophy (FSHD) is one of the most common hereditary myodystrophies. A study of the genetic nature of the disease, which has an autosomal dominant mode of inheritance, is extremely interesting and revealing. A unique structure of D4Z4 macrosatellite repeats found in the 4q35 region was originally characterized by a decrease in the number of repeats in patients with Landouzy–Dejerine muscular dystrophy, which resulted in the activation of neighboring genes, in particular, the DUX4 transcription factor. Later, it was found that the epigenetic mechanisms responsible for the chromatin condensation of this region underlie the activation. To date, additional participants leading to pathogenesis of the disease, such as SMCHD1 methylation regulator and DBE-T regulatory long noncoding RNA, have been identified. The revealed complexity of the disease mechanisms is in good agreement with the observed pattern of the disease inheritance. The study of the Landouzy–Dejerine muscular dystrophy pathogenesis is a good example of how monogenic diseases can possess a more complex nature of inheritance.

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References

  1. 1.

    Padberg, G.W., Frants, R.R., Brouwer, O.F., et al., Facioscapulohumeral muscular dystrophy in the Dutch population, Muscle Nerve Suppl., 1995, vol. 2, pp. S81–S84.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Flanigan, K.M., Coffeen, C.M., Sexton, L., et al., Genetic characterization of a large, historically significant Utah kindred with facioscapulohumeral dystrophy, Neuromuscular Disord., 2001, vol. 11, nos. 6–7, pp. 525–529.

    CAS  Article  Google Scholar 

  3. 3.

    Mostacciuolo, M.L., Pastorello, E., Vazza, G., et al., Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north-east Italian population sample, Clin. Genet., 2009, vol. 75, no. 6, pp. 550–555. doi 10.1111/j.1399-0004.2009.01158.x

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Norwood, F.L., Harling, C., Chinnery, P.F., et al., Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population, Brain, 2009, vol. 132, no. 11, pp. 3175–3186. doi 10.1093/brain/awp236

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Zatz, M., Marie, S.K., Passos-Bueno, M.R., et al., High proportion of new mutations and possible anticipation in Brazilian facioscapulohumeral muscular dystrophy families, Am. J. Hum. Genet., 1995, vol. 56, no. 1, pp. 99–105.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Bakker, E., Wijmenga, C., Vossen, R.H., et al., The FSHD-linked locus D4F104S1 (p13E-11) on 4q35 has a homologue on 10qter, Muscle Nerve Suppl., 1995, vol. 2, pp. S39–S44.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Landouzy, L. and Dejerine, J., De la myopathie atrophique progressive; myopathie héréditaire, sans neuropathie, debutant d’ordinaire dans l’enfance par la face, Paris: F. Alcan, 1885.

    Google Scholar 

  8. 8.

    Padberg, G., Facioscapulohumeral Disease, Leiden: Univ. Leiden, 1982.

    Google Scholar 

  9. 9.

    Tawil, R., Storvick, D., Feasby, T.E., et al., Extreme variability of expression in monozygotic twins with FSH muscular dystrophy, Neurology, 1993, vol. 43, no. 2, pp. 345–348.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Padberg, G.W., Facioscapulohumeral muscular dystrophy: a clinician’s experience, in Facioscapulohumeral Muscular Dystrophy (FSHD): Clinical Medicine and Molecular Cell Biology, London: Garland Science, 2004, pp. 41–51.

    Google Scholar 

  11. 11.

    Tawil, R., Facioscapulohumeral muscular dystrophy, Neurotherapeutics, 2008, vol. 5, no. 4, pp. 601–606. doi 10.1016/j.nurt.2008.07.005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Quarantelli, M., Lanzillo, R., Del Vecchio, W., et al., Modifications of brain tissue volumes in facioscapulohumeral dystrophy, Neuroimage, 2006, vol. 32, no. 3, pp. 1237–1242. doi 10.1016/j.neuroimage.2006.04.226

    Article  PubMed  Google Scholar 

  13. 13.

    Arahata, K., Ishihara, T., Fukunaga, H., et al., Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD): immunocytochemical and genetic analyses, Muscle Nerve Suppl., 1995, vol. 2, pp. S56–S66.

    Google Scholar 

  14. 14.

    Frisullo, G., Frusciante, R., Nociti, V., et al., CD8(+) T cells in facioscapulohumeral muscular dystrophy patients with inflammatory features at muscle MRI, J. Clin. Immunol., 2011, vol. 31, no. 2, pp. 155–166. doi 10.1007/s10875-010-9474-6

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Papa, S., Guerrieri, F., Zanotti, F., et al., F0 and F1 subunits involved in the gate and coupling function of mitochondrial H+ ATP synthase, Ann. N.Y. Acad. Sci., 1992, vol. 671, pp. 345–358.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Upadhyaya, M., Lunt, P.W., Sarfarazi, M., et al., DNA marker applicable to presymptomatic and prenatal diagnosis of facioscapulohumeral disease, Lancet, 1990, vol. 336, no. 8726, pp. 1320–1321.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Wijmenga, C., Frants, R.R., Brouwer, O.F., et al., Location of facioscapulohumeral muscular dystrophy gene on chromosome 4, Lancet, 1990, vol. 336, no. 8716, pp. 651–653.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Wijmenga, C., Padberg, G.W., Moerer, P., et al., Mapping of facioscapulohumeral muscular dystrophy gene to chromosome 4q35-qter by multipoint linkage analysis and in situ hybridization, Genomics, 1991, vol. 9, no. 4, pp. 570–575.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Mathews, K.D., Mills, K.A., Bosch, E.P., et al., Linkage localization of facioscapulohumeral muscular dystrophy (FSHD) in 4q35, Am. J. Hum. Genet., 1992, vol. 51, no. 2, pp. 428–431.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Upadhyaya, M., Lunt, P., Sarfarazi, M., et al., The mapping of chromosome 4q markers in relation to facioscapulohumeral muscular dystrophy (FSHD), Am. J. Hum. Genet., 1992, vol. 51, no. 2, pp. 404–410.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Wijmenga, C., Hewitt, J.E., Sandkuijl, L.A., et al., Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy, Nat. Genet., 1992, vol. 2, no. 1, pp. 26–30. doi 10.1038/ng0992-26

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Gabriels, J., Beckers, M.C., Ding, H., et al., Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element, Gene, 1999, vol. 236, no. 1, pp. 25–32.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Deidda, G., Cacurri, S., Grisanti, P., et al., Physical mapping evidence for a duplicated region on chromosome 10qter showing high homology with the facioscapulohumeral muscular dystrophy locus on chromosome 4qter, Eur. J. Hum. Genet., 1995, vol. 3, no. 3, pp. 155–167.

    CAS  PubMed  Google Scholar 

  24. 24.

    Butz, M., Koch, M.C., Muller-Felber, W., et al., Facioscapulohumeral muscular dystrophy: phenotypegenotype correlation in patients with borderline D4Z4 repeat numbers, J. Neurol., 2003, vol. 250, no. 8, pp. 932–937. doi 10.1007/s00415-003-1116-y

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Lunt, P.W., 44th ENMC International Workshop: Facioscapulohumeral Muscular Dystrophy: Molecular Studies 19–21 July 1996, Naarden, The Netherlands, Neuromuscular Disord., 1998, vol. 8, no. 2, pp. 126–130.

    CAS  Article  Google Scholar 

  26. 26.

    Bakker, E., Wijmenga, C., Vossen, R.H., et al., The FSHD-linked locus D4F104S1 (p13E-11) on 4q35 has a homologue on 10qter, Muscle Nerve Suppl., 1995, vol. 2, pp. S39–S44.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Lemmers, R.J., van der Maarel, S.M., van Deutekom, J.C., et al., Inter- and intrachromosomal sub-telomeric rearrangements on 4q35: implications for facioscapulohumeral muscular dystrophy (FSHD) aetiology and diagnosis, Hum. Mol. Genet., 1998, vol. 7, no. 8, pp. 1207–1214.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Lemmers, R.J., Wohlgemuth, M., van der Gaag, K.J., et al., Specific sequence variations within the 4q35 region are associated with facioscapulohumeral muscular dystrophy, Am. J. Hum. Genet., 2007, vol. 81, no. 5, pp. 884–894. doi 10.1086/521986

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Lemmers, R.J., van der Vliet, P.J., van der Gaag, K.J., et al., Worldwide population analysis of the 4q and 10q subtelomeres identifies only four discrete interchromosomal sequence transfers in human evolution, Am. J. Hum. Genet., 2010, vol. 86, no. 3, pp. 364–377. doi 10.1016/j.ajhg.2010.01.035

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Wijmenga, C., Frants, R.R., Hewitt, J.E., et al., Molecular genetics of facioscapulohumeral muscular dystrophy, Neuromuscular Disord., 1993, vol. 3, nos. 5–6, pp. 487–491.

    CAS  Article  Google Scholar 

  31. 31.

    Tupler, R., Berardinelli, A., Barbierato, L., et al., Monosomy of distal 4q does not cause facioscapulohumeral muscular dystrophy, J. Med. Genet., 1996, vol. 33, no. 5, pp. 366–370.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Hewitt, J.E., Lyle, R., Clark, L.N., et al., Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy, Hum. Mol. Genet., 1994, vol. 3, no. 8, pp. 1287–1295.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Snider, L., Asawachaicharn, A., Tyler, A.E., et al., RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: new candidates for the pathophysiology of facioscapulohumeral dystrophy, Hum. Mol. Genet., 2009, vol. 18, no. 13, pp. 2414–2430. doi 10.1093/hmg/ddp180

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Dixit, M., Ansseau, E., Tassin, A., et al., DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1, Proc. Natl. Acad. Sci. U.S.A., 2007, vol. 104, no. 46, pp. 18157–18162. doi 10.1073/pnas.0708659104

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    van Geel, M., Dickson, M.C., Beck, A.F., et al., Genomic analysis of human chromosome 10q and 4q telomeres suggests a common origin, Genomics, 2002, vol. 79, no. 2, pp. 210–217. doi 10.1006/geno. 2002.6690

    Article  PubMed  Google Scholar 

  36. 36.

    Lejeune, E. and Allshire, R.C., Common ground: small RNA programming and chromatin modifications, Curr. Opin. Cell. Biol., 2011, vol. 23, no. 3, pp. 258–265. doi 10.1016/j.ceb.2011.03.005

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Pal-Bhadra, M., Leibovitch, B.A., Gandhi, S.G., et al., Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery, Science, 2004, vol. 303, no. 5658, pp. 669–672. doi 10.1126/science.1092653

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Probst, A.V., Okamoto, I., Casanova, M., et al., A strand-specific burst in transcription of pericentric satellites is required for chromocenter formation and early mouse development, Dev. Cell, 2010, vol. 19, no. 4, pp. 625–638. doi 10.1016/j.devcel.2010.09.002

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Sabin, L.R., Delas, M.J., and Hannon, G.J., Dogma derailed: the many influences of RNA on the genome, Mol Cell, 2013, vol. 49, no. 5, pp. 783–794. doi 10.1016/j.molcel.2013.02.010

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Volpe, T.A., Kidner, C., Hall, I.M., et al., Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi, Science, 2002, vol. 297, no. 5588, pp. 1833–1837. doi 10.1126/science.1074973

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Snider, L., Geng, L.N., Lemmers, R.J., et al., Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene, PLoS Genet., 2010, vol. 6, no. 10. e1001181. doi 10.1371/journal.pgen.1001181

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Cabianca, D.S., Casa, V., Bodega, B., et al., A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy, Cell, 2012, vol. 149, no. 4, pp. 819–831. doi 10.1016/j.cell.2012.03.035

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Gregory, G.D., Vakoc, C.R., Rozovskaia, T., et al., Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes, Mol. Cell. Biol., 2007, vol. 27, no. 24, pp. 8466–8479. doi 10.1128/MCB.00993-07

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Tanaka, Y., Katagiri, Z., Kawahashi, K., et al., Trithorax- group protein ASH1 methylates histone H3 lysine 36, Gene, 2007, vol. 397, nos. 1–2, pp. 161–168. doi 10.1016/j.gene.2007.04.027

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Yuan, W., Xu, M., Huang, C., et al., H3K36 methylation antagonizes PRC2-mediated H3K27 methylation, J. Biol. Chem., 2011, vol. 286, no. 10, pp. 7983–7989. doi 10.1074/jbc.M110.194027

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Tassin, A., Laoudj-Chenivesse, D., Vanderplanck, C., et al., DUX4 expression in FSHD muscle cells: how could such a rare protein cause a myopathy?. J. Cell. Mol. Med., 2013, vol. 17, no. 1, pp. 76–89. doi 10.1111/j.1582-4934.2012.01647.x

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Bourque, G., Leong, B., Vega, V.B., et al., Evolution of the mammalian transcription factor binding repertoire via transposable elements, Genome Res., 2008, vol. 18, no. 11, pp. 1752–1762. doi 10.1101/gr.080663.108

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Leidenroth, A. and Hewitt, J.E., A family history of DUX4: phylogenetic analysis of DUXA, B, C and Duxbl reveals the ancestral DUX gene, BMC Evol. Biol., 2010, vol. 10, p. 364. doi 10.1186/1471-2148-10- 364

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    van Overveld, P.G., Lemmers, R.J., Sandkuijl, L.A., et al., Hypomethylation of D4Z4 in 4q-linked and non- 4q-linked facioscapulohumeral muscular dystrophy, Nat. Genet., 2003, vol. 35, no. 4, pp. 315–317. doi 10.1038/ng1262

    Article  PubMed  Google Scholar 

  50. 50.

    de Greef, J.C., Lemmers, R.J., van Engelen, B.G., et al., Common epigenetic changes of D4Z4 in contraction- dependent and contraction-independent FSHD, Hum. Mutat., 2009, vol. 30, no. 10, pp. 1449–1459. doi 10.1002/humu.21091

    Article  PubMed  Google Scholar 

  51. 51.

    Zeng, W., de Greef, J.C., Chen, Y.Y., et al., Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD), PLoS Genet., 2009, vol. 5, no. 7. e1000559. doi 10.1371/journal.pgen.1000559

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Balog, J., Thijssen, P.E., de Greef, J.C., et al., Correlation analysis of clinical parameters with epigenetic modifications in the DUX4 promoter in FSHD, Epigenetics, 2012, vol. 7, no. 6, pp. 579–584. doi 10.4161/epi.20001

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Kowaljow, V., Marcowycz, A., Ansseau, E., et al., The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein, Neuromuscular Disord., 2007, vol. 17, no. 8, pp. 611–623. doi 10.1016/j.nmd.2007.04.002

    Article  Google Scholar 

  54. 54.

    Wallace, L.M., Garwick, S.E., Mei, W., et al., DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo, Ann. Neurol., 2011, vol. 69, no. 3, pp. 540–552. doi 10.1002/ana.22275

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Lemmers, R.J., Tawil, R., Petek, L.M., et al., Digenic inheritance of an SMCHD1 mutation and an FSHDpermissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2, Nat. Genet., 2012, vol. 44, no. 12, pp. 1370–1374. doi 10.1038/ng.2454

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Blewitt, M.E., Gendrel, A.V., Pang, Z., et al., SmcHD1, containing a structural-maintenance-ofchromosomes hinge domain, has a critical role in X inactivation, Nat. Genet., 2008, vol. 40, no. 5, pp. 663–669. doi 10.1038/ng.142

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Gendrel, A.V., Apedaile, A., Coker, H., et al., Smchd1- dependent and-independent pathways determine developmental dynamics of CpG island methylation on the inactive X chromosome, Dev. Cell, 2012, vol. 23, no. 2, pp. 265–279. doi 10.1016/j.devcel.2012.06.011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Gendrel, A.V., Tang, Y.A., Suzuki, M., et al., Epigenetic functions of smchd1 repress gene clusters on the inactive X chromosome and on autosomes, Mol. Cell. Biol., 2013, vol. 33, no. 16, pp. 3150–3165. doi 10.1128/MCB.00145-13

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Mould, A.W., Pang, Z., Pakusch, M., et al., Smchd1 regulates a subset of autosomal genes subject to monoallelic expression in addition to being critical for X inactivation, Epigenet. Chromatin, 2013, vol. 6, no. 1, pp. 19. doi 10.1186/1756-8935-6-19

    CAS  Article  Google Scholar 

  60. 60.

    Larsen, M., Rost, S., El Hajj, N., et al., Diagnostic approach for FSHD revisited: SMCHD1 mutations cause FSHD2 and act as modifiers of disease severity in FSHD1, Eur. J. Hum. Genet., 2015, vol. 23, no. 6, pp. 808–816. doi 10.1038/ejhg.2014.191

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Lunt, P.W., Compston, D.A., and Harper, P.S., Estimation of age dependent penetrance in facioscapulohumeral muscular dystrophy by minimising ascertainment bias, J. Med. Genet., 1989, vol. 26, no. 12, pp. 755–760.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Scionti, I., Greco, F., Ricci, G., et al., Large-scale population analysis challenges the current criteria for the molecular diagnosis of fascioscapulohumeral muscular dystrophy, Am. J. Hum. Genet., 2012, vol. 90, no. 4, pp. 628–635. doi 10.1016/j.ajhg.2012.02.019

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Statland, J.M., McDermott, M.P., Heatwole, C., et al., Reevaluating measures of disease progression in facioscapulohumeral muscular dystrophy, Neuromuscular Disord., 2013, vol. 23, no. 4, pp. 306–312. doi 10.1016/j.nmd.2013.01.008

    Article  Google Scholar 

  64. 64.

    The FSH-DY Group, A prospective, quantitative study of the natural history of facioscapulohumeral muscular dystrophy (FSHD): implications for therapeutic trials, Neurology, 1997, vol. 48, no. 1, pp. 38–46.

    Article  Google Scholar 

  65. 65.

    Busse, K., Kohler, J., Stegmann, K., et al., An inherited 4q35-EcoRI-DNA-fragment of 35 kb in a family with a sporadic case of facioscapulohumeral muscular dystrophy (FSHD), Neuromuscular Disord., 2000, vol. 10, no. 3, pp. 178–181.

    CAS  Article  Google Scholar 

  66. 66.

    Tsumagari, K., Chen, D., Hackman, J.R., et al., FSH dystrophy and a subtelomeric 4q haplotype: a new assay and associations with disease, J. Med. Genet., 2010, vol. 47, no. 11, pp. 745–751. doi 10.1136/jmg.2009.076703

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67.

    de Greef, J.C., Frants, R.R., and van der Maarel, S.M., Epigenetic mechanisms of facioscapulohumeral muscular dystrophy, Mutat. Res., 2008, vol. 647, nos. 1–2, pp. 94–102. doi 10.1016/j.mrfmmm.2008.07.011

    Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Jones, T.I., Yan, C., Sapp, P.C., et al., Identifying diagnostic DNA methylation profiles for facioscapulohumeral muscular dystrophy in blood and saliva using bisulfite sequencing, Clin. Epigenet., 2014, vol. 6, no. 1, p. 23. doi 10.1186/1868-7083-6-23

    Article  Google Scholar 

  69. 69.

    Nguyen, K., Walrafen, P., Bernard, R., et al., Molecular combing reveals allelic combinations in facioscapulohumeral dystrophy, Ann. Neurol., 2011, vol. 70, no. 4, pp. 627–633. doi 10.1002/ana.22513

    CAS  Article  PubMed  Google Scholar 

  70. 70.

    Vasale, J., Boyar, F., Jocson, M., et al., Molecular combing compared to Southern blot for measuring D4Z4 contractions in FSHD, Neuromuscular Disord., 2015, vol. 25, no. 12, pp. 945–951. doi 10.1016/j.nmd. 2015.08.008

    Article  Google Scholar 

  71. 71.

    Newlands, S., Levitt, L.K., Robinson, C.S., et al., Transcription occurs in pulses in muscle fibers, Genes Dev., 1998, vol. 12, no. 17, pp. 2748–2758.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to M. Yu. Skoblov.

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Original Russian Text © N.V. Zernov, A.V. Marakhonov, J.V. Vyakhireva, A.A. Guskova, E.L. Dadali, M.Yu. Skoblov, 2017, published in Genetika, 2017, Vol. 53, No. 6, pp. 651–662.

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Zernov, N.V., Marakhonov, A.V., Vyakhireva, J.V. et al. Clinical and genetic characteristics and diagnostic features of Landouzy–Dejerine facioscapulohumeral muscular dystrophy. Russ J Genet 53, 640–650 (2017). https://doi.org/10.1134/S102279541706014X

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Keywords

  • Landouzy–Dejerine muscular dystrophy
  • pathogenesis of the disease
  • DNA diagnostics