Academic Journal
The Biallelic Inheritance of Two Novel SCN1A Variants Results in Developmental and Epileptic Encephalopathy Responsive to Levetiracetam
| العنوان: | The Biallelic Inheritance of Two Novel SCN1A Variants Results in Developmental and Epileptic Encephalopathy Responsive to Levetiracetam |
|---|---|
| المؤلفون: | Giorgia Dinoi, Elena Conte, Orazio Palumbo, Mario Benvenuto, Maria Antonietta Coppola, Pietro Palumbo, Patrizia Lastella, Brigida Boccanegra, Ester Di Muro, Marco Castori, Massimo Carella, Vittorio Sciruicchio, Marina de Tommaso, Antonella Liantonio, Annamaria De Luca, Angela La Neve, Paola Imbrici |
| المصدر: | Biomedicines, Vol 12, Iss 8, p 1698 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | SCN1A, Nav1.1, epilepsy, patch-clamp, biallelic inheritance, Biology (General), QH301-705.5 |
| الوصف: | Loss-, gain-of-function and mixed variants in SCN1A (Nav1.1 voltage-gated sodium channel) have been associated with a spectrum of neurologic disorders with different severity and drug-responsiveness. Most SCN1A variants are heterozygous changes occurring de novo or dominantly inherited; recessive inheritance has been reported in a few cases. Here, we report a family in which the biallelic inheritance of two novel SCN1A variants, N935Y and H1393Q, occurs in two siblings presenting with drug-responsive developmental and epileptic encephalopathy and born to heterozygous asymptomatic parents. To assess the genotype–phenotype correlation and support the treatment choice, HEK 293 cells were transfected with different combinations of the SCN1A WT and mutant cDNAs, and the resulting sodium currents were recorded through whole-cell patch-clamp. Functional studies showed that the N935Y and H1393Q channels and their combinations with the WT (WT + N935Y and WT + H1393Q) had current densities and biophysical properties comparable with those of their respective control conditions. This explains the asymptomatic condition of the probands’ parents. The co-expression of the N935Y + H1393Q channels, mimicking the recessive inheritance of the two variants in siblings, showed ~20% reduced current amplitude compared with WT and with parental channels. This mild loss of Nav1.1 function may contribute in part to the disease pathogenesis, although other mechanisms may be involved. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 12081698 2227-9059 |
| Relation: | https://www.mdpi.com/2227-9059/12/8/1698; https://doaj.org/toc/2227-9059 |
| DOI: | 10.3390/biomedicines12081698 |
| URL الوصول: | https://doaj.org/article/1301cdd3bed04a10ad83ef8e40aba0bf |
| رقم الانضمام: | edsdoj.1301cdd3bed04a10ad83ef8e40aba0bf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 12081698 22279059 |
|---|---|
| DOI: | 10.3390/biomedicines12081698 |