Clinical and molecular characterization of myotonia congenita using whole-exome sequencing in Egyptian patients.
Mol Biol Rep
; 51(1): 766, 2024 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-38877370
ABSTRACT
BACKGROUND:
Myotonia Congenita (MC) is a rare disease classified into two major forms; Thomsen and Becker disease caused by mutations in the CLCN1 gene, which affects muscle excitability and encodes voltage-gated chloride channels (CLC-1). While, there are no data regarding the clinical and molecular characterization of myotonia in Egyptian patients.METHODS:
Herein, we report seven Egyptian MC patients from six unrelated families. Following the clinical diagnosis, whole-exome sequencing (WES) was performed for genetic diagnosis. Various in silico prediction tools were utilized to interpret variant pathogenicity. The candidate variants were then validated using Sanger sequencing technique.RESULTS:
In total, seven cases were recruited. The ages at the examination were ranged from eight months to nineteen years. Clinical manifestations included warm-up phenomenon, hand grip, and percussion myotonia. Electromyography was performed in all patients and revealed myotonic discharges. Molecular genetic analysis revealed five different variants. Of them, we identified two novel variants in the CLCN1 gene ( c.1583G > C; p.Gly528Ala and c.2203_2216del;p.Thr735ValfsTer57) and three known variants in the CLCN1 and SCN4A gene. According to in silico tools, the identified novel variants were predicted to have deleterious effects.CONCLUSIONS:
As the first study to apply WES among Egyptian MC patients, our findings reported two novel heterozygous variants that expand the CLCN1 mutational spectrum for MC diagnosis. These results further confirm that genetic testing is essential for early diagnosis of MC, which affects follow-up treatment and prognostic assessment in clinical practice.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Canales de Cloruro
/
Secuenciación del Exoma
/
Mutación
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Miotonía Congénita
Límite:
Adolescent
/
Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
País/Región como asunto:
Africa
Idioma:
En
Revista:
Mol Biol Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Egipto
Pais de publicación:
Países Bajos