Identification of a novel homozygous SCN1B splice-site variant in a consanguineous families with early-onset epilepsy: A case series and review of literature

Authors

• Anees Muhammad, Khyber Medical University
• Shafaq Ramzan, Aga Khan UniversityFollow
• Hammad Yousaf, Aga Khan UniversityFollow
• Rafia Zafar Ghumman, Islam Medical College, Sialkot
• Farhan Bahadar Ali, Peshawar Medical College
• Muhammad Athar Khalily, Northwest General Hospital and Research Center
• Asmat Ali, Aga Khan UniversityFollow
• Wajid Ali, University of Swat
• Salma Zia, Aga Khan University
• Najeeb Ullah Khan, The University of Agriculture Peshawar
• Muhammad Tahir Sarwar, Khyber Medical University
• Matias Toft, University of Oslo
• Zafar Iqbal, Oslo University Hospital
• Ambrin Fatima, Aga Khan UniversityFollow

Document Type

Review Article

Department

Biological and Biomedical Sciences

Abstract

Background: Pathogenic variants in SCN1B, the gene encoding the sodium channel β1 subunit, are associated with generalized epilepsy with febrile seizures plus (GEFS+) and related epilepsy disorders. These disorders exhibit phenotypic heterogeneity and varying clinical severity under autosomal dominant as well as recessive inheritance models. The current study investigated the genetic basis of epilepsy in two consanguineous Pakistani families.
Methods: We investigated two unrelated Pakistani families with four affected individuals presenting with early-onset epilepsy. Exome sequencing (ES) was performed in the index cases in both families to identify the underlying genetic cause. Sanger sequencing was used for validation and segregation analysis in additional family members.
Results: The affected individuals presented overlapping clinical features including early-onset drug-refractory seizures, developmental delay, intellectual disability, and autism spectrum disorder. ES identified a novel homozygous canonical splice-site variant in SCN1B (NM_001037.5): c.591-2A>G p.(?) in all affected individuals.
Conclusions: A novel homozygous SCN1B splice site variant was identified in two unrelated consanguineous families as the most likely cause of the early-onset epilepsy. These findings underscore the importance of genetic screening and tailored therapeutic strategies in epilepsy management.

Publication (Name of Journal)

Molecular Genetics & Genomic Medicine

DOI

10.1002/mgg3.70214

Recommended Citation

Muhammad, A., Ramzan, S., Yousaf, H., Ghumman, R. Z., Ali, F. B., Khalily, M. A., Ali, A., Ali, W., Zia, S., Khan, N. U., Sarwar, M. T., Toft, M., Iqbal, Z., Fatima, A. (2026). Identification of a novel homozygous SCN1B splice-site variant in a consanguineous families with early-onset epilepsy: A case series and review of literature. Molecular Genetics & Genomic Medicine, 14(5), 1-7.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_bbs/1115