Clinical and molecular characterization of myotonia congenita using whole-exome sequencing in Egyptian patients.

Autor: Elaraby NM; Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Dokki, Cairo, Egypt. nesma172@yahoo.com., Ahmed HA; Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Dokki, Cairo, Egypt., Dawoud H; Pediatric Department, Tanta University, Gharbia, Egypt., Ashaat NA; Professor of Human Genetics, Ain Shams University, Cairo, Egypt., Azmy A; Child Health Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, Egypt., Galal ER; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Elhusseny Y; Lecturer of Medical Biochemistry and Molecular Biology, School of Medicine, Newgiza University, Giza, Egypt., Awady HE; Pediatric Department, Fayoum University Hospitals, Fayoum, Egypt., Metwally AM; Community Medicine Research Department/Medical Research, Clinical Studies Institute/National Research Centre (Affiliation ID: 60014618), Dokki, Cairo, Egypt., Ashaat EA; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 Jun 15; Vol. 51 (1), pp. 766. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1007/s11033-024-09646-8
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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