Retrospective analysis of persistent HyperCKemia with or without muscle weakness in a case series from Greece highlights vast DMD variant heterogeneity.
| Title: | Retrospective analysis of persistent HyperCKemia with or without muscle weakness in a case series from Greece highlights vast DMD variant heterogeneity. |
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| Authors: | Kekou K; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Svingou M; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Vogiatzakis N; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Nitsa E; Postgraduate Program in Biostatistics School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; Veltra D; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; St. Sophia's Children's Hospital, Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, National and Kapodistrian University of Athens, Athens, Greece.; Marinakis NM; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; St. Sophia's Children's Hospital, Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, National and Kapodistrian University of Athens, Athens, Greece.; Tilemis FN; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Tzetis M; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Mitrakos A; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; St. Sophia's Children's Hospital, Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, National and Kapodistrian University of Athens, Athens, Greece.; Tsaroucha C; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Selenti N; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Papadimas GK; Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Papadopoulos C; Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Traeger-Synodinos J; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Lochmuller H; Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Freiburg, Germany.; Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Children's Hospital of Eastern Ontario Research Institute; Division of Neurology, Department of Medicine, The Ottawa Hospital, Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada.; Sofocleous C; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. |
| Source: | Expert review of molecular diagnostics [Expert Rev Mol Diagn] 2023 Jul-Dec; Vol. 23 (11), pp. 999-1010. Date of Electronic Publication: 2023 Oct 24. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 101120777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-8352 (Electronic) Linking ISSN: 14737159 NLM ISO Abbreviation: Expert Rev Mol Diagn Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : Abingdon, Oxford : Taylor & Francis; Original Publication: London : Future Drugs Ltd, 2001- |
| MeSH Terms: | Dystrophin*/genetics ; Muscular Dystrophy, Duchenne*/diagnosis; Greece/epidemiology ; Humans ; Male ; Guanine Nucleotide Exchange Factors ; Muscle Weakness ; Nucleotides ; Retrospective Studies |
| Abstract: | Background: Persistent hyperCKemia results from muscle dysfunction often attributed to genetic alterations of muscle-related genes, such as the dystrophin gene (DMD). Retrospective assessment of findings from DMD analysis, in association with persistent HyperCKemia, was conducted.; Patients and Methods: Evaluation of medical records from 1354 unrelated cases referred during the period 1996-2021. Assessment of data concerning the detection of DMD gene rearrangements and nucleotide variants.; Results: A total of 730 individuals (657 cases, 569 of Greek and 88 of Albanian origins) were identified, allowing an overall estimation of dystrophinopathy incidence at ~1:3800 live male births. The heterogeneous spectrum of 275 distinct DMD alterations comprised exon(s) deletions/duplications, nucleotide variants, and rare events, such as chromosome translocation {t(X;20)}, contiguous gene deletions, and a fused gene involving the DMD and the DOCK8 genes. Ethnic-specific findings include a common founder variant in exon 36 ('Hellenic' variant).; Conclusions: Some 50% of hyperCKemia cases were characterized as dystrophinopathies, highlighting that DMD variants may be considered the most common cause of hyperCKemia in Greece. Delineation of the broad genetic and clinical heterogeneity is fundamental for actionable public health decisions and theragnosis, as well as the establishment of guidelines addressing ethical considerations, especially related to the mild asymptomatic patient subgroup. |
| Contributed Indexing: | Keywords: Duchenne; Dystrophin; creatine kinase; epidemiology; hyperCKemia case series |
| Substance Nomenclature: | 0 (DOCK8 protein, human); 0 (Dystrophin); 0 (Guanine Nucleotide Exchange Factors); 0 (Nucleotides); 0 (DMD protein, human) |
| Entry Date(s): | Date Created: 20230927 Date Completed: 20231030 Latest Revision: 20231030 |
| Update Code: | 20260130 |
| DOI: | 10.1080/14737159.2023.2264181 |
| PMID: | 37754746 |
| Database: | MEDLINE |
Journal Article