دورية أكاديمية
أعرض في EDS

Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.

التفاصيل البيبلوغرافية
العنوان: Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.
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).)
References: Pediatr Neurol. 2014 Dec;51(6):806-813.e8. (PMID: 25456301)
J Neurosci Res. 2012 Dec;90(12):2306-16. (PMID: 22847264)
Genet Med. 2021 May;23(5):900-908. (PMID: 33473208)
Autophagy. 2019 Jan;15(1):34-57. (PMID: 30081747)
Front Mol Neurosci. 2022 Jun 17;15:877258. (PMID: 35782384)
Front Cell Dev Biol. 2021 Jun 25;9:644947. (PMID: 34249907)
Brain. 2014 Jul;137(Pt 7):1907-20. (PMID: 24833714)
NPJ Genom Med. 2018 Mar 27;3:9. (PMID: 29619247)
Genet Med. 2015 May;17(5):405-24. (PMID: 25741868)
Hum Mutat. 2016 Jan;37(1):127-34. (PMID: 26467025)
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33. (PMID: 25431634)
Eur J Med Genet. 2017 Aug;60(8):437-443. (PMID: 28602933)
Genet Mol Biol. 2017 Jul-Sep;40(3):591-596. (PMID: 28863211)
Int J Neurosci. 2019 Dec;129(12):1198-1202. (PMID: 31385551)
Neurology. 2009 Oct 6;73(14):1111-9. (PMID: 19805727)
Genes (Basel). 2021 Sep 26;12(10):. (PMID: 34680907)
Am J Med Genet B Neuropsychiatr Genet. 2009 Oct 5;150B(7):993-7. (PMID: 19160445)
Hum Mol Genet. 2012 Apr 15;21(8):1725-43. (PMID: 22186024)
Mov Disord. 2015 May;30(6):770-9. (PMID: 25900096)
FEBS Lett. 2017 Jan;591(1):196-204. (PMID: 27926783)
Clin Genet. 2018 Mar;93(3):671-674. (PMID: 28892125)
Seizure. 2017 Feb;45:125-131. (PMID: 28024199)
J Neurol. 2022 Jul;269(7):3789-3799. (PMID: 35166927)
Brain. 2013 Oct;136(Pt 10):3119-39. (PMID: 24030950)
J Neurol. 2014 Feb;261(2):435-7. (PMID: 24366652)
Expert Rev Neurother. 2020 Dec;20(12):1207-1209. (PMID: 33084433)
Mol Vis. 2009;15:801-9. (PMID: 19390655)
Matrix Biol. 2017 Jan;57-58:55-75. (PMID: 27746220)
Gene. 2023 Aug 30;879:147599. (PMID: 37393059)
J Biol Chem. 2011 Aug 26;286(34):29654-62. (PMID: 21724849)
Hum Mutat. 2011 Aug;32(8):956-64. (PMID: 21542062)
Trends Cell Biol. 2019 Dec;29(12):974-986. (PMID: 31703843)
Ophthalmic Genet. 2020 Feb;41(1):83-87. (PMID: 32178553)
Nat Genet. 2011 Jun;43(6):585-9. (PMID: 21572417)
Genes (Basel). 2021 Nov 19;12(11):. (PMID: 34828430)
FEBS Lett. 2013 May 2;587(9):1316-25. (PMID: 23499937)
Lancet Neurol. 2020 Jan;19(1):93-100. (PMID: 31494011)
J Biol Chem. 2007 Feb 23;282(8):5256-62. (PMID: 17182609)
Neurocase. 2022 Feb;28(1):11-18. (PMID: 35253627)
Int J Clin Exp Pathol. 2020 Jul 01;13(7):1853-1858. (PMID: 32782714)
Bone Rep. 2023 May 04;18:101683. (PMID: 37214758)
Eur J Ophthalmol. 2021 Nov;31(6):3349-3354. (PMID: 33238767)
J Gastrointest Surg. 2023 Jan;27(1):56-66. (PMID: 36127552)
JAMA Ophthalmol. 2016 Jul 1;134(7):753-62. (PMID: 27259167)
Epilepsia. 2010 Jun;51(6):1069-77. (PMID: 19889013)
Mov Disord. 2010 Sep 15;25(12):1929-37. (PMID: 20683840)
Eur J Med Genet. 2020 Nov;63(11):104021. (PMID: 32755715)
Hum Mol Genet. 2012 Jun 15;21(12):2646-50. (PMID: 22388936)
Brain. 2017 Feb;140(2):287-305. (PMID: 28137957)
J Formos Med Assoc. 2022 Jan;121(1 Pt 1):126-133. (PMID: 33637369)
Hum Genomics. 2019 Apr 16;13(1):19. (PMID: 30992063)
Science. 2007 Apr 20;316(5823):445-9. (PMID: 17363630)
Am J Hum Genet. 2002 Dec;71(6):1320-9. (PMID: 12415512)
Mol Syndromol. 2016 Sep;7(4):210-219. (PMID: 27781031)
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
الوصف
تدمد:1471-2377
DOI:10.1186/s12883-024-03671-7