Retrospective analysis of persistent HyperCKemia with or without muscle weakness in a case series from Greece highlights vast DMD variant heterogeneity

References

• Kyriakides T, Angelini C, Schaefer J, et al. EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCkemia. Eur J Neurol. 2010;17(6):767–773. doi: 10.1111/j.1468-1331.2010.03012.x
   PubMed Web of Science ®Google Scholar
• Prelle A, Tancredi L, Sciacco M, et al. Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels. J Neurol. 2002;249(3):305–311. doi: 10.1007/s004150200010
   PubMed Web of Science ®Google Scholar
• Al-Ghamdi F, Darras BT, Ghosh PS. Spectrum of neuromuscular disorders with HyperCKemia from a tertiary care pediatric neuromuscular center. J Child Neurol. 2018;33(6):389–396. doi: 10.1177/0883073818758455
   PubMed Web of Science ®Google Scholar
• Rubegni A, Malandrini A, Dosi C, et al. Next-generation sequencing approach to hyperCkemia: a 2-year cohort study. Neurol Genet. 2019;5(5):e352. doi: 10.1212/NXG.0000000000000352
   PubMed Web of Science ®Google Scholar
• Kyriakides T, Angelini C, Vilchez J, et al. European Federation of the Neurological Societies guidelines on the diagnostic approach to paucisymptomatic or asymptomatic hyperCkemia. Muscle Nerve. 2020;61(2):E14–E15. doi: 10.1002/mus.26777
   PubMed Web of Science ®Google Scholar
• Lilleng H, Abeler K, Johnsen SH, et al. Variation of serum creatine kinase (CK) levels and prevalence of persistent hyperCkemia in a Norwegian normal population. The tromsø study. Neuromuscular Disorders. 2011;21(7):494–500. doi: 10.1016/j.nmd.2011.04.007
   PubMed Web of Science ®Google Scholar
• Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2(12):731–740. doi: 10.1016/S1474-4422(03)00585-4
   PubMed Web of Science ®Google Scholar
• Bies RD, Phelps SF, Cortez MD, et al. Human and murine dystrophin mRNA transcripts are differentially expressed during skeletal muscle, heart, and brain development. Nucleic Acids Res. 1992;20(7):1725–1731. doi: 10.1093/nar/20.7.1725
   PubMed Web of Science ®Google Scholar
• Tuffery-Giraud S, Béroud C, Leturcq F, et al. Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Hum Mutat. 2009;30(6):934–945. doi: 10.1002/humu.20976
   PubMed Web of Science ®Google Scholar
• Bladen CL, Salgado D, Monges S, et al. The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat. 2015;36(4):395–402. doi: 10.1002/humu.22758
   PubMed Web of Science ®Google Scholar
• Neri M, Rossi R, Trabanelli C, et al. The genetic landscape of dystrophin mutations in Italy: a nationwide study. Front Genet. 2020;11:131. doi: 10.3389/fgene.2020.00131
   PubMed Web of Science ®Google Scholar
• Ma P, Zhang S, Zhang H, et al. Comprehensive genetic characteristics of dystrophinopathies in China. Orphanet J Rare Dis. 2018 4;13(1):109. Erratum in: Orphanet J Rare Dis. 2021 Jun; 16(1):252. doi: 10.1186/s13023-018-0853-z
   PubMedGoogle Scholar
• Juan-Mateu J, Gonzalez-Quereda L, Rodriguez MJ, et al. DMD mutations in 576 dystrophinopathy families: a step forward in genotype-phenotype correlations. Plos One. 2015;10(8):e0135189. doi: 10.1371/journal.pone.0135189
   PubMed Web of Science ®Google Scholar
• Okubo M, Goto K, Komaki H, et al. Comprehensive analysis for genetic diagnosis of dystrophinopathies in Japan. Orphanet J Rare Dis. 2017;12(1):149. doi: 10.1186/s13023-017-0703-4
   PubMedGoogle Scholar
• Kohli S, Saxena R, Thomas E, et al. Mutation spectrum of dystrophinopathies in India: implications for therapy. Indian J Pediatr. 2020;87(7):495–504. doi: 10.1007/s12098-020-03286-z
   PubMed Web of Science ®Google Scholar
• Mah JK, Selby K, Campbell C, et al. A population-based study of dystrophin mutations in Canada. Can J Neurol Sci. 2011;38(3):465–474. doi: 10.1017/S0317167100011896
   PubMed Web of Science ®Google Scholar
• Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for molecular Pathology. Genet Med [Internet]. 2015;17(5):405–424. doi: 10.1038/gim.2015.30
   PubMed Web of Science ®Google Scholar
• Bailey M, Miller N. DMD Open-access variant Explorer (DOVE): a scalable, open-access, web-based tool to aid in clinical interpretation of genetic variants in the DMD gene. Mol Genet Genomic Med. 2019;7:e00510. doi: 10.1002/mgg3.510
   PubMed Web of Science ®Google Scholar
• Florentin L, Mavrou A, Kekou K, et al. Deletion patterns of Duchenne and Becker muscular dystrophies in Greece. J Med Genet. 1995;32(1):48–51. doi: 10.1136/jmg.32.1.48
   PubMed Web of Science ®Google Scholar
• Kekou K, Mavrou A, Florentin L, et al. Screening for minor changes in the distal part of the human dystrophin gene in Greek DMD/BMD patients. Eur J Hum Genet. 1999;7(2):179–187. doi: 10.1038/sj.ejhg.5200253
   PubMed Web of Science ®Google Scholar
• Kekou K, Sofocleous C, Papadimas G, et al. A dynamic trinucleotide repeat (TNR) expansion in the DMD gene. Mol Cell Probes. 2016;30(4):254–260. doi: 10.1016/j.mcp.2016.07.001
   PubMed Web of Science ®Google Scholar
• Pons R, Kekou K, Gkika A, et al. Single amino acid loss in the dystrophin protein associated with a mild clinical phenotype. Muscle Nerve. 2017;55(1):46–50. doi: 10.1002/mus.25190
   PubMed Web of Science ®Google Scholar
• Marinakis NM, Svingou M, Veltra D, et al. Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders. Am J Med Genet A. 2021;185(8):2561–2571. doi: 10.1002/ajmg.a.62338
   PubMed Web of Science ®Google Scholar
• Kokotis P, Papadimas GK, Zouvelou V, et al. Electrodiagnosis and muscle biopsy in asymptomatic hyperckemia. Int J Neurosci. 2016;126(6):514–519. doi: 10.3109/00207454.2015.1038534
   PubMed Web of Science ®Google Scholar
• Keegan NP. Pseudoexons of the DMD gene. J Neuromuscul Dis. 2020;7(2):77–95. doi: 10.3233/JND-190431
   PubMedGoogle Scholar
• Hellenic Statistical Authority. Provisional Results of the Census of Housing for 2021. 2021.
   Google Scholar
• Wahlgren L, Kroksmark A-K, Tulinius M, et al. One in five patients with Duchenne muscular dystrophy dies from other causes than cardiac or respiratory failure. Eur J Epidemiol. 2022;37(2):147–156. doi: 10.1007/s10654-021-00819-4
   PubMed Web of Science ®Google Scholar
• Rall S, Grimm T. Survival in Duchenne muscular dystrophy. Acta Myol Myopathies Cardiomyopathies Off J Mediterr Soc Myol. 2012;31:117–120.
   PubMedGoogle Scholar
• Broomfield J, Hill M, Guglieri M, et al. Life expectancy in Duchenne muscular dystrophy: reproduced individual patient data meta-analysis. Neurology. 2021;97(23):e2304–e2314. doi: 10.1212/WNL.0000000000012910
   PubMed Web of Science ®Google Scholar
• Töpf A, Johnson K, Bates A, et al. Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness. Genet Med. 2020;22(9):1478–1488. doi: 10.1038/s41436-020-0840-3
   PubMed Web of Science ®Google Scholar
• Boyd Y, Buckle V, Holt S, et al. Muscular dystrophy in girls with X;autosome translocations. J Med Genet. 1986;23:484–490. doi: 10.1136/jmg.23.6.484
   PubMed Web of Science ®Google Scholar
• Takeshima Y, Yagi M, Okizuka Y, et al. Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J Hum Genet. 2010;55(6):379–388. doi: 10.1038/jhg.2010.49
   PubMed Web of Science ®Google Scholar
• Viggiano E, Ergoli M, Picillo E, et al. Determining the role of skewed X-chromosome inactivation in developing muscle symptoms in carriers of Duchenne muscular dystrophy. Hum Genet. 2016;135(7):685–698. doi: 10.1007/s00439-016-1666-6
   PubMed Web of Science ®Google Scholar
• Crisafulli S, Sultana J, Fontana A, et al. Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis. 2020;15(1):141. doi: 10.1186/s13023-020-01430-8
   PubMed Web of Science ®Google Scholar
• Bushby KM, Thambyayah M, Gardner-Medwin D. Prevalence and incidence of Becker muscular dystrophy. Lancet (London, England). 1991;337:1022–1024. doi: 10.1016/0140-6736(91)92671-N
   PubMed Web of Science ®Google Scholar
• Chien Y-H, Lee N-C, Weng W-C, et al. Duchenne muscular dystrophy newborn screening: the first 50,000 newborns screened in Taiwan. Neurol Sci. 2022;43(7):4563–4566. doi: 10.1007/s10072-022-06128-2
   PubMed Web of Science ®Google Scholar
• Gatheridge MA, Kwon JM, Mendell JM, et al. Identifying non-Duchenne muscular dystrophy-positive and false negative results in prior Duchenne muscular dystrophy newborn screening programs: a review. JAMA Neurol. 2016;73:111–116. doi: 10.1001/jamaneurol.2015.3537
   PubMed Web of Science ®Google Scholar
• Okubo M, Noguchi S, Hayashi S, et al. Exon skipping induced by nonsense/frameshift mutations in DMD gene results in Becker muscular dystrophy. Hum Genet. 2020;139(2):247–255. doi: 10.1007/s00439-019-02107-4
   PubMed Web of Science ®Google Scholar
• Florczyk-Soluch U, Polak K, Dulak J. The multifaceted view of heart problem in Duchenne muscular dystrophy. Cell Mol Life Sci. 2021;78(14):5447–5468. doi: 10.1007/s00018-021-03862-2
   PubMed Web of Science ®Google Scholar
• da ST, Anequini IP, Fávero FM, et al. Functional performance and muscular strength in symptomatic female carriers of Duchenne muscular dystrophy. Arq Neuropsiquiatr. 2020;78:143–148. doi: 10.1590/0004-282x20190168
   PubMed Web of Science ®Google Scholar
• Counterman KJ, Furlong P, Wang RT, et al. Delays in diagnosis of Duchenne muscular dystrophy: an evaluation of genotypic and sociodemographic factors. Muscle Nerve. 2020;61(1):36–43. doi: 10.1002/mus.26720
   PubMed Web of Science ®Google Scholar
• Deng J, Zhang J, Shi K, et al. Drug development progress in Duchenne muscular dystrophy. Front Pharmacol. 2022;13:950651. doi: 10.3389/fphar.2022.950651
   PubMed Web of Science ®Google Scholar
• Sun C, Shen L, Zhang Z, et al. Therapeutic strategies for Duchenne Muscular Dystrophy: an update. Genes (Basel). 2020;11(8):11. doi: 10.3390/genes11080837
   Web of Science ®Google Scholar
• Markati T, Oskoui M, Farrar MA, et al. Emerging therapies for Duchenne muscular dystrophy. Lancet Neurol. 2022;21(9):814–829. doi: 10.1016/S1474-4422(22)00125-9
   PubMed Web of Science ®Google Scholar
• Moat SJ, Bradley DM, Salmon R, et al. Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK). Eur J Hum Genet. 2013;21(10):1049–1053. doi: 10.1038/ejhg.2012.301
   PubMed Web of Science ®Google Scholar