{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rodan LH"],"funding":["Ministry of Education and Research of the Community of Madrid","NICHD NIH HHS","NIMH NIH HHS","NHGRI NIH HHS","National Institutes of Health"],"pagination":["1922-1932"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8488020"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(10)"],"pubmed_abstract":["<h4>Purpose</h4>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.<h4>Methods</h4>We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.<h4>Results</h4>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 experi"],"journal":["Genetics in medicine : official journal of the American College of Medical Genetics"],"pubmed_title":["Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations."],"pmcid":["PMC8488020"],"funding_grant_id":["R01 HD090132","F32 HG000130","R01 HG009141","B2017/BMD-3721","U01HG007672","U01 HG007672","U01 MH119689","U01 HG007709","U01HG007709","UM1 HG008900"],"pubmed_authors":["Dasari S","Cole FS","Undiagnosed Diseases Network","Lachmeijer G","Liu XZ","Emrick LT","Santos-Simarro F","Solem E","Wener M","Murdock DR","Novacic D","Gutierrez I","Malicdan MCV","Sutton S","Lincoln SA","Eliyahu A","Cunningham M","Wang HG","Amendola L","Walker M","Butte MJ","Stoler JM","Emrick L","Dickson P","Santani A","Moretti PM","Bonner D","Woods JD","Kozuira M","Cooper CM","Smith EC","Loo SK","Hahn S","Coakley TR","Pallais JC","Fieg EL","Papp JC","Acosta MT","Kelley EG","Posey JE","Chang TCP","Nagy A","Lanza IR","Silverman EK","Latham L","Forghani I","Dayal JG","Jarvik GP","Vogel TP","Adams DR","Deardorff M","Krakow D","Duncan L","Zhao C","Byers P","Martin MG","Azamian MS","Vincent M","Fisher PG","Bale J","Fogel BL","Renteria G","Groden CA","Antonarakis SE","Sinsheimer JS","Lanpher BC","Scott DA","Macchiaiolo M","Roulet-Perez E","McCray AT","Whitlock J","Findley LC","Newman JH","Scott CR","Sweetser DA","Huryn L","Pacio-Miguez M","Adam M","Alvey J","Tran AA","Macnamara EF","Gochuico B","Carrasquillo O","Rush E","Cobban LA","Nickerson D","Pusey BN","Berg-Rood B","Davis J","Mosbrook-Davis D","Kurata HT","Marth G","Bjorgo K","Schaechter J","Wang LK","Cogan JD","Nicholas SK","Bivona S","Tabor HK","Wenger T","Bejerano G","Dhar SU","Van Bogaert P","Granadillo JL","Jarvik J","Craigen WJ","Might M","Boyd B","Kennedy J","Isasi R","Zein W","Tucker BM","Zacher P","Wangler MF","Karaviti L","Pak S","Zuchner S","Hisama FM","Bayrak-Toydemir P","Martin BA","Longo N","Hayes N","Rosenfeld JA","Skraban C","Jamal F","Mao R","Liu P","Sullivan K","Mamounas LA","Wallace S","Wambach J","Maghera J","Lalani SR","Thurm A","Dorrani N","Parker NH","Blue E","Palmer CGS","Engleman K","Saporta M","Orengo JP","Thorson W","Telischi F","Wheeler MT","Hing A","Horike-Pyne M","Au PYB","Good JM","Martinez-Agosto JA","Bennett J","Atallah I","Bamshad M","Pena L","Tekin M","Eng CM","van Jaabrsveld RH","D'Souza P","Odent S","Hom J","Kravets E","Fresard L","Draper DD","Nelson SF","Smith KS","LaMoure GL","Sybert V","Walsh CA","Krasnewich DM","Urv TK","Bohnsack J","Tifft CJ","Wan J","Baldridge D","Lewis RA","Holm IA","Sacco R","Solnica-Krezel L","Clark GD","Markello TC","Mak BC","McCauley J","Rodan LH","McCormack CE","Kohane IS","Byrd WE","Nieves-Rodriguez S","Beck A","Perry KW","Samson SL","Potocki L","Moretti P","Grajewski A","Crouse AB","Glass I","Wegner D","Doss AL","Donald KA","Rives L","Coggins M","Dubourg C","Andrews A","Kiley D","Kohler JN","Ben Solomon","Lee H","Shashi V","Jamra RA","Behrens E","O'Heir E","Nath A","Botto L","Ashley EA","Platzer K","Blanc X","Bacino CA","Chanprasert S","Majcherska MM","Alejandro ME","Eckstein DJ","Barbouth D","MacDowall J","Briere LC","Superti-Furga A","Ferreira C","Fernandez L","Quinlan A","Krier JB","Ruzhnikov M","Lamothe SM","Signer RH","Agrawal PB","Maravilla K","Beggs AH","Marwaha S","Nakano-Okuno M","Huang Y","Thiffault I","Bonnenmann C","Hamid R","Pode-Shakked B","Zastrow DB","Reuter CM","Dai H","Spillmann RC","Raja AN","Sisco K","Sun A","Ranza E","Vanderver A","Burrage LC","Slaugh R","Balasubramanyam A","Shin J","Schoch K","Baker E","Brown G","Palomares-Bralo M","Marom R","Kalser J","Manolio TA","Toro C","Bolkier Y","Pace L","Lee BH","Goldrich MP","Chao HT","Esteves C","Oglesbee D","Huang A","Hanchard NA","Yang J","Velinder M","Nicita F","Pitt GS","McConkie-Rosell A","Morava E","Yousef M","Maduro VV","Yamamoto S","Viskochil D","Carey J","Goldman AM","Sampson JB","Levitt R","Merritt JL","Bademci G","Falk M","High F","Quinodoz M","Bernstein JA","Berry GT","Burke EA","Bican A","Kloeckner C","Brokamp E","Goldstein DB","LeBlanc K","Lam B","Walley NM","Rossignol F","Lam C","Robertson AK","Hassey K","Cope H","Ward PA","Gonfiantini MV","Earl D","McGee E","MacRae CA","Christ BU","Mefford H","Sullivan JA","Doherty D","Mirzaa G","PhillipsIII JA","Bilan F","Power B","Alkelai A","Rosenwasser N","Bar-Yosef O","Maas RL","Loscalzo J","Colley HA","Mulvihill JJ","Gahl WA","Schedl T","Ortiz-Gonzalez X","Rao DA","Jayadev S","Dipple K","Wolfe LA","Korrick S","Raskind W","Dell'Angelica EC","Tan QK","Godfrey RA","Westerfield M","Wahl CE","Douine ED","Golden-Grant K"],"additional_accession":[]},"is_claimable":false,"name":"Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations.","description":"<h4>Purpose</h4>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.<h4>Methods</h4>We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.<h4>Results</h4>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 experi","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-05-09T04:16:48.809Z","creation":"2025-02-18T23:36:21.654Z"},"accession":"S-EPMC8488020","cross_references":{"pubmed":["34163037"],"doi":["10.1038/s41436-021-01232-8"]}}