De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Segal A) > De Novo Pathogenic ...

Details
MARC

Helbig, K. L. (author)

De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias

Article/chapterEnglish2018

Publisher, publication year, extent ...

Elsevier BV,2018

Numbers

LIBRIS-ID:oai:gup.ub.gu.se/273681
https://gup.ub.gu.se/publication/273681URI
https://doi.org/10.1016/j.ajhg.2018.09.006DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:139492388URI

Supplementary language notes

Language:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
calcium-channel dysfunction
r-type
molecular pathology
ilae
commission
position paper
ca2+ channels
mice lacking
disorders
mutations
classification
Genetics & Heredity

Added entries (persons, corporate bodies, meetings, titles ...)

Lauerer, R. J. (author)
Bahr, J. C. (author)
Souza, I. A. (author)
Myers, C. T. (author)
Uysal, B. (author)
Schwarz, N. (author)
Gandini, M. A. (author)
Huang, S. (author)
Keren, B. (author)
Mignot, C. (author)
Afenjar, A. (author)
de Villemeur, T. B. (author)
Heron, D. (author)
Nava, C. (author)
Valence, S. (author)
Buratti, J. (author)
Fagerberg, C. R. (author)
Soerensen, K. P. (author)
Kibaek, M. (author)
Kamsteeg, E. J. (author)
Koolen, D. A. (author)
Gunning, B. (author)
Schelhaas, H. J. (author)
Kruer, M. C. (author)
Fox, J. (author)
Bakhtiari, S. (author)
Jarrar, R. (author)
Padilla-Lopez, S. (author)
Lindstrom, K. (author)
Jin, S. C. (author)
Zeng, X. (author)
Bilguvar, K. (author)
Papavasileiou, A. (author)
Xin, Q. H. (author)
Zhu, Changlian,1964Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xzhuch (author)
Boysen, K. (author)
Vairo, F. (author)
Lanpher, B. C. (author)
Klee, E. W. (author)
Tillema, J. M. (author)
Payne, E. T. (author)
Cousin, M. A. (author)
Kruisselbrink, T. M. (author)
Wick, M. J. (author)
Baker, J. (author)
Haan, E. (author)
Smith, N. (author)
Corbett, M. A. (author)
MacLennan, A. H. (author)
Gecz, J. (author)
Biskup, S. (author)
Goldmann, E. (author)
Rodan, L. H. (author)
Kichula, E. (author)
Segal, E. (author)
Jackson, K. E. (author)
Asamoah, A. (author)
Dimmock, D. (author)
McCarrier, J. (author)
Botto, L. D. (author)
Filloux, F. (author)
Tvrdik, T. (author)
Cascino, G. D. (author)
Klingerman, S. (author)
Neumann, C. (author)
Wang, R. (author)
Jacobsen, J. C. (author)
Nolan, M. A. (author)
Snell, R. G. (author)
Lehnert, K. (author)
Sadleir, L. G. (author)
Anderlid, B. M.Karolinska Institutet (author)
Kvarnung, M.Karolinska Institutet (author)
Guerrini, R. (author)
Friez, M. J. (author)
Lyons, M. J. (author)
Leonhard, J. (author)
Kringlen, G. (author)
Casas, K. (author)
El Achkar, C. M. (author)
Smith, L. A. (author)
Rotenberg, A. (author)
Poduri, A. (author)
Sanchis-Juan, A. (author)
Carss, K. J. (author)
Rankin, J. (author)
Zeman, A. (author)
Raymond, F. L. (author)
Blyth, M. (author)
Kerr, B. (author)
Ruiz, K. (author)
Urquhart, J. (author)
Hughes, I. (author)
Banka, S. (author)
Hedrich, U. B. S. (author)
Scheffer, I. E. (author)
Helbig, I. (author)
Zamponi, G. W. (author)
Lerche, H. (author)
Mefford, H. C. (author)
Deciphering Dev Disorders, Study (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi (creator_code:org_t)

Related titles

In:American Journal of Human Genetics: Elsevier BV103:5, s. 666-6780002-92971537-6605

Internet link

Find in a library

American Journal of Human Genetics (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Helbig, K. L.; Lauerer, R. J.; Bahr, J. C.; Souza, I. A.; Myers, C. T.; Uysal, B.; show more...; Schwarz, N.; Gandini, M. A.; Huang, S.; Keren, B.; Mignot, C.; Afenjar, A.; de Villemeur, T. ...; Heron, D.; Nava, C.; Valence, S.; Buratti, J.; Fagerberg, C. R.; Soerensen, K. P.; Kibaek, M.; Kamsteeg, E. J.; Koolen, D. A.; Gunning, B.; Schelhaas, H. J.; Kruer, M. C.; Fox, J.; Bakhtiari, S.; Jarrar, R.; Padilla-Lopez, S ...; Lindstrom, K.; Jin, S. C.; Zeng, X.; Bilguvar, K.; Papavasileiou, A ...; Xin, Q. H.; Zhu, Changlian, ...; Boysen, K.; Vairo, F.; Lanpher, B. C.; Klee, E. W.; Tillema, J. M.; Payne, E. T.; Cousin, M. A.; Kruisselbrink, T ...; Wick, M. J.; Baker, J.; Haan, E.; Smith, N.; Corbett, M. A.; MacLennan, A. H.; Gecz, J.; Biskup, S.; Goldmann, E.; Rodan, L. H.; Kichula, E.; Segal, E.; Jackson, K. E.; Asamoah, A.; Dimmock, D.; McCarrier, J.; Botto, L. D.; Filloux, F.; Tvrdik, T.; Cascino, G. D.; Klingerman, S.; Neumann, C.; Wang, R.; Jacobsen, J. C.; Nolan, M. A.; Snell, R. G.; Lehnert, K.; Sadleir, L. G.; Anderlid, B. M.; Kvarnung, M.; Guerrini, R.; Friez, M. J.; Lyons, M. J.; Leonhard, J.; Kringlen, G.; Casas, K.; El Achkar, C. M.; Smith, L. A.; Rotenberg, A.; Poduri, A.; Sanchis-Juan, A.; Carss, K. J.; Rankin, J.; Zeman, A.; Raymond, F. L.; Blyth, M.; Kerr, B.; Ruiz, K.; Urquhart, J.; Hughes, I.; Banka, S.; Hedrich, U. B. S ...; Scheffer, I. E.; Helbig, I.; Zamponi, G. W.; Lerche, H.; Mefford, H. C.; Deciphering Dev ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Articles in the publication: American Journal ...

By the university: University of Gothenburg; Karolinska Institutet

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se