دورية أكاديمية
Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.
العنوان: | Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families. |
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المؤلفون: | Yasin M; Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, 26000, Pakistan., Licchetta L; RCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy., Khan N; Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, 26000, Pakistan., Ullah I; Department of Neurology, Khyber Teaching Hospital, Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan., Jan Z; Department of Neurology, Pakistan Institute of Medical Science, Islamabad, 44000, Pakistan., Dawood M; Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, 26000, Pakistan., Ahmed AN; Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, 26000, Pakistan., Azeem A; Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, 26000, Pakistan., Minardi R; RCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy., Carelli V; RCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. valerio.carelli@unibo.it.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. valerio.carelli@unibo.it., Saleha S; Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, 26000, Pakistan. shamimsaleha@yahoo.com. |
المصدر: | BMC neurology [BMC Neurol] 2024 May 23; Vol. 24 (1), pp. 172. Date of Electronic Publication: 2024 May 23. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100968555 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2377 (Electronic) Linking ISSN: 14712377 NLM ISO Abbreviation: BMC Neurol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, [2001- |
مواضيع طبية MeSH: | Epilepsy*/genetics , Epilepsy*/epidemiology , Epilepsy*/diagnosis , Comorbidity* , Genetic Heterogeneity* , Pedigree*, Humans ; Pakistan/epidemiology ; Male ; Female ; Child ; Child, Preschool ; Adolescent ; Exome Sequencing ; Adult ; Developmental Disabilities/genetics ; Developmental Disabilities/epidemiology ; Young Adult ; Intellectual Disability/genetics ; Intellectual Disability/epidemiology ; Phenotype |
مستخلص: | Background: Epilepsy, a challenging neurological condition, is often present with comorbidities that significantly impact diagnosis and management. In the Pakistani population, where financial limitations and geographical challenges hinder access to advanced diagnostic methods, understanding the genetic underpinnings of epilepsy and its associated conditions becomes crucial. Methods: This study investigated four distinct Pakistani families, each presenting with epilepsy and a spectrum of comorbidities, using a combination of whole exome sequencing (WES) and Sanger sequencing. The epileptic patients were prescribed multiple antiseizure medications (ASMs), yet their seizures persist, indicating the challenging nature of ASM-resistant epilepsy. Results: Identified genetic variants contributed to a diverse range of clinical phenotypes. In the family 1, which presented with epilepsy, developmental delay (DD), sleep disturbance, and aggressive behavior, a homozygous splice site variant, c.1339-6 C > T, in the COL18A1 gene was detected. The family 2 exhibited epilepsy, intellectual disability (ID), DD, and anxiety phenotypes, a homozygous missense variant, c.344T > A (p. Val115Glu), in the UFSP2 gene was identified. In family 3, which displayed epilepsy, ataxia, ID, DD, and speech impediment, a novel homozygous frameshift variant, c.1926_1941del (p. Tyr643MetfsX2), in the ZFYVE26 gene was found. Lastly, family 4 was presented with epilepsy, ID, DD, deafness, drooling, speech impediment, hypotonia, and a weak cry. A homozygous missense variant, c.1208 C > A (p. Ala403Glu), in the ATP13A2 gene was identified. Conclusion: This study highlights the genetic heterogeneity in ASM-resistant epilepsy and comorbidities among Pakistani families, emphasizing the importance of genotype-phenotype correlation and the necessity for expanded genetic testing in complex clinical cases. (© 2024. The Author(s).) |
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معلومات مُعتمدة: | 1-8/HEC/HRD/2022/8802/PIN: IRSIP 50 BMS 40 Higher Education Commision, Pakistan |
فهرسة مساهمة: | Keywords: ASM-resistant epilepsy; Clinical profiles; Comorbidities; Genetic heterogeneity; Pakistani families |
تواريخ الأحداث: | Date Created: 20240523 Date Completed: 20240524 Latest Revision: 20240526 |
رمز التحديث: | 20240526 |
مُعرف محوري في PubMed: | PMC11112905 |
DOI: | 10.1186/s12883-024-03671-7 |
PMID: | 38783254 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1471-2377 |
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DOI: | 10.1186/s12883-024-03671-7 |