Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations.
Détails
ID Serval
serval:BIB_1C202819AA37
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations.
Périodique
Genetics in medicine
Collaborateur⸱rice⸱s
Undiagnosed Diseases Network
Contributeur⸱rice⸱s
Alejandro M.E., Azamian M.S., Bacino C.A., Balasubramanyam A., Burrage L.C., Chao H.T., Clark G.D., Craigen W.J., Dai H., Dhar S.U., Emrick L.T., Goldman A.M., Hanchard N.A., Jamal F., Karaviti L., Lalani S.R., Lee B.H., Lewis R.A., Marom R., Moretti P.M., Murdock D.R., Nicholas S.K., Orengo J.P., Posey J.E., Potocki L., Rosenfeld J.A., Samson S.L., Scott D.A., Tran A.A., Vogel T.P., Wangler M.F., Yamamoto S., Eng C.M., Liu P., Ward P.A., Behrens E., Deardorff M., Falk M., Hassey K., Sullivan K., Vanderver A., Goldstein D.B., Cope H., McConkie-Rosell A., Schoch K., Shashi V., Smith E.C., Spillmann R.C., Sullivan J.A., Tan Q.K., Walley N.M., Agrawal P.B., Beggs A.H., Berry G.T., Briere L.C., Cobban L.A., Coggins M., Cooper C.M., Fieg E.L., High F., Holm I.A., Korrick S., Krier J.B., Lincoln S.A., Loscalzo J., Maas R.L., MacRae C.A., Pallais J.C., Rao D.A., Rodan L.H., Silverman E.K., Stoler J.M., Sweetser D.A., Walker M., Walsh C.A., Esteves C., Kelley E.G., Kohane I.S., LeBlanc K., McCray A.T., Nagy A., Dasari S., Lanpher B.C., Lanza I.R., Morava E., Oglesbee D., Bademci G., Barbouth D., Bivona S., Carrasquillo O., Chang TCP, Forghani I., Grajewski A., Isasi R., Lam B., Levitt R., Liu X.Z., McCauley J., Sacco R., Saporta M., Schaechter J., Tekin M., Telischi F., Thorson W., Zuchner S., Colley H.A., Dayal J.G., Eckstein D.J., Findley L.C., Krasnewich D.M., Mamounas L.A., Manolio T.A., Mulvihill J.J., LaMoure G.L., Goldrich M.P., Urv T.K., Doss A.L., Acosta M.T., Bonnenmann C., D'Souza P., Draper D.D., Ferreira C., Godfrey R.A., Groden C.A., Macnamara E.F., Maduro V.V., Markello T.C., Nath A., Novacic D., Pusey B.N., Toro C., Wahl C.E., Baker E., Burke E.A., Adams D.R., Gahl W.A., Malicdan MCV, Tifft C.J., Wolfe L.A., Yang J., Power B., Gochuico B., Huryn L., Latham L., Davis J., Mosbrook-Davis D., Rossignol F., Ben Solomon s, MacDowall J., Thurm A., Zein W., Yousef M., Adam M., Amendola L., Bamshad M., Beck A., Bennett J., Berg-Rood B., Blue E., Boyd B., Byers P., Chanprasert S., Cunningham M., Dipple K., Doherty D., Earl D., Glass I., Golden-Grant K., Hahn S., Hing A., Hisama F.M., Horike-Pyne M., Jarvik G.P., Jarvik J., Jayadev S., Lam C., Maravilla K., Mefford H., Merritt J.L., Mirzaa G., Nickerson D., Raskind W., Rosenwasser N., Scott C.R., Sun A., Sybert V., Wallace S., Wener M., Wenger T., Ashley E.A., Bejerano G., Bernstein J.A., Bonner D., Coakley T.R., Fernandez L., Fisher P.G., Fresard L., Hom J., Huang Y., Kohler J.N., Kravets E., Majcherska M.M., Martin B.A., Marwaha S., McCormack C.E., Raja A.N., Reuter C.M., Ruzhnikov M., Sampson J.B., Smith K.S., Sutton S., Tabor H.K., Tucker B.M., Wheeler M.T., Zastrow D.B., Zhao C., Byrd W.E., Crouse A.B., Might M., Nakano-Okuno M., Whitlock J., Brown G., Butte M.J., Dell'Angelica E.C., Dorrani N., Douine E.D., Fogel B.L., Gutierrez I., Huang A., Krakow D., Lee H., Loo S.K., Mak B.C., Martin M.G., Martínez-Agosto J.A., McGee E., Nelson S.F., Nieves-Rodriguez S., Palmer CGS, Papp J.C., Parker N.H., Renteria G., Signer R.H., Sinsheimer J.S., Wan J., Wang L.K., Perry K.W., Woods J.D., Alvey J., Andrews A., Bale J., Bohnsack J., Botto L., Carey J., Pace L., Longo N., Marth G., Moretti P., Quinlan A., Velinder M., Viskochil D., Bayrak-Toydemir P., Mao R., Westerfield M., Bican A., Brokamp E., Duncan L., Hamid R., Kennedy J., Kozuira M., Newman J.H., PhillipsIII J.A., Rives L., Robertson A.K., Solem E., Cogan J.D., Cole F.S., Hayes N., Kiley D., Sisco K., Wambach J., Wegner D., Baldridge D., Pak S., Schedl T., Shin J., Solnica-Krezel L.
ISSN
1530-0366 (Electronic)
ISSN-L
1098-3600
Statut éditorial
Publié
Date de publication
10/2021
Peer-reviewed
Oui
Volume
23
Numéro
10
Pages
1922-1932
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.
We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.
Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.
We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.
We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.
Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.
We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.
Mots-clé
Autistic Disorder/genetics, Calcium Channels, L-Type/genetics, Humans, Long QT Syndrome, Phenotype, Syndactyly
Pubmed
Web of science
Création de la notice
06/07/2021 15:34
Dernière modification de la notice
20/07/2022 16:54
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