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Retrospective analysis of persistent HyperCKemia with or without muscle weakness in a case series from Greece
Kyriaki Kekou1, Maria Svingou1, Nikos Vogiatzakis1
1Laboratory of Medical Genetics, St. Sophia's Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Insights
Persistent hyperCKemia is often caused by genetic mutations in the dystrophin gene (DMD). This study found DMD variants are the most common cause of hyperCKemia in Greece, impacting public health decisions.
Area of Science:
- Genetics
- Molecular Biology
- Neuromuscular Disorders
Background:
- Persistent hyperCKemia often stems from muscle dysfunction linked to genetic alterations in muscle-related genes, notably the dystrophin gene (DMD).
- A retrospective analysis focused on DMD gene alterations in patients with persistent hyperCKemia.
Purpose of the Study:
- To assess the prevalence and spectrum of DMD gene alterations in individuals with persistent hyperCKemia.
- To determine the contribution of DMD variants to hyperCKemia in the Greek population.
Main Methods:
- Medical records of 1354 unrelated cases referred between 1996 and 2021 were evaluated.
- Data on DMD gene rearrangements and nucleotide variants were collected and analyzed.
Main Results:
- Dystrophinopathy incidence was estimated at approximately 1:3800 live male births among 730 identified individuals.
- A diverse range of 275 distinct DMD alterations were identified, including deletions, duplications, nucleotide variants, and rare events like translocations and fused genes.
- A founder variant in exon 36, termed the 'Hellenic' variant, was noted in individuals of Greek origin.
Conclusions:
- Approximately 50% of hyperCKemia cases were identified as dystrophinopathies, establishing DMD variants as a primary cause of hyperCKemia in Greece.
- Understanding the genetic and clinical heterogeneity of these conditions is crucial for public health strategies, theranostics, and ethical guidelines, particularly for asymptomatic individuals.
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.
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