Purpose: Genetics of Sleep-related Hypermotor Epilepsy (SHE) includes mutations in several genes that cumulatively account for 30 % of families. This approximate estimate comes from different case-series, each focused on the screening of a single gene. We systematically investigated a large cohort of SHE patients to estimate the frequency of pathogenic variants in the main genes thus far implicated in this epilepsy syndrome. Methods: We selected familial and isolated cases diagnosed with clinical/confirmed SHE who underwent genetic analysis by comparable next generation sequencing (NGS) techniques (WES/ multigene epilepsy panel). The identified heterozygous variants were classified according to the American College of Medical Genetics and Genomics guidelines. Results: We included 103 SHE patients (M/F:61/42) who underwent NGS. Sixteen (15.5 %) were familial cases, 16.5 % had focal cortical dysplasia (FCD). We identified three pathogenic variants in CHRNA4 (2.9 %, CI: 0.6–8.3 %), two of whom novel; one pathogenic variant in KCNT1 (1 %, CI: 0.02–5.29 %); four loss-of-function variants in DEPDC5 (3.9 %, CI: 1.1–9.7 %), one of whom never reported; finally, one missense change in NPRL2 (1 %, CI: 0.02–5.29 %), already reported as pathogenic. Three out of the four patients with DEPDC5 variants had FCD. Conclusions: The overall frequency of pathogenic variants in our SHE cohort was 8.7 %, 19 % and 7 % considering familial and sporadic cases, respectively. Pathogenic variants in the GATOR1-complex genes account for 5 % of the cases. DEPDC5 shows the highest variants frequency, especially in patients with genetic-structural etiology. From a practical perspective, analysis of this gene is recommended even in isolated cases, because of possible implications for patient management.

Sleep-related hypermotor epilepsy (SHE): Contribution of known genes in 103 patients / Licchetta, L.; Pippucci, T.; Baldassari, S.; Minardi, R.; Provini, F.; Mostacci, B.; Plazzi, G.; Tinuper, P.; Bisulli, F.; Bianchi, A.; Striano, P.; Gambardella, A.; Giordano, L.; Santucci, M.; Meletti, S.; Crichiutti, G.; Marini, C.; Vignoli, A.; Dilena, R.; Briatore, E.. - In: SEIZURE. - ISSN 1059-1311. - 74:(2020), pp. 60-64. [10.1016/j.seizure.2019.11.009]

Sleep-related hypermotor epilepsy (SHE): Contribution of known genes in 103 patients

Baldassari S.;Minardi R.;Plazzi G.;Bisulli F.;Gambardella A.;Meletti S.;
2020

Abstract

Purpose: Genetics of Sleep-related Hypermotor Epilepsy (SHE) includes mutations in several genes that cumulatively account for 30 % of families. This approximate estimate comes from different case-series, each focused on the screening of a single gene. We systematically investigated a large cohort of SHE patients to estimate the frequency of pathogenic variants in the main genes thus far implicated in this epilepsy syndrome. Methods: We selected familial and isolated cases diagnosed with clinical/confirmed SHE who underwent genetic analysis by comparable next generation sequencing (NGS) techniques (WES/ multigene epilepsy panel). The identified heterozygous variants were classified according to the American College of Medical Genetics and Genomics guidelines. Results: We included 103 SHE patients (M/F:61/42) who underwent NGS. Sixteen (15.5 %) were familial cases, 16.5 % had focal cortical dysplasia (FCD). We identified three pathogenic variants in CHRNA4 (2.9 %, CI: 0.6–8.3 %), two of whom novel; one pathogenic variant in KCNT1 (1 %, CI: 0.02–5.29 %); four loss-of-function variants in DEPDC5 (3.9 %, CI: 1.1–9.7 %), one of whom never reported; finally, one missense change in NPRL2 (1 %, CI: 0.02–5.29 %), already reported as pathogenic. Three out of the four patients with DEPDC5 variants had FCD. Conclusions: The overall frequency of pathogenic variants in our SHE cohort was 8.7 %, 19 % and 7 % considering familial and sporadic cases, respectively. Pathogenic variants in the GATOR1-complex genes account for 5 % of the cases. DEPDC5 shows the highest variants frequency, especially in patients with genetic-structural etiology. From a practical perspective, analysis of this gene is recommended even in isolated cases, because of possible implications for patient management.
23-nov-2019
74
60
64
Sleep-related hypermotor epilepsy (SHE): Contribution of known genes in 103 patients / Licchetta, L.; Pippucci, T.; Baldassari, S.; Minardi, R.; Provini, F.; Mostacci, B.; Plazzi, G.; Tinuper, P.; Bisulli, F.; Bianchi, A.; Striano, P.; Gambardella, A.; Giordano, L.; Santucci, M.; Meletti, S.; Crichiutti, G.; Marini, C.; Vignoli, A.; Dilena, R.; Briatore, E.. - In: SEIZURE. - ISSN 1059-1311. - 74:(2020), pp. 60-64. [10.1016/j.seizure.2019.11.009]
Licchetta, L.; Pippucci, T.; Baldassari, S.; Minardi, R.; Provini, F.; Mostacci, B.; Plazzi, G.; Tinuper, P.; Bisulli, F.; Bianchi, A.; Striano, P.; Gambardella, A.; Giordano, L.; Santucci, M.; Meletti, S.; Crichiutti, G.; Marini, C.; Vignoli, A.; Dilena, R.; Briatore, E.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1196076
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