Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations - Université de Rennes Access content directly
Journal Articles Genetics in Medicine Year : 2021

Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

Lance Rodan (1) , Rebecca Spillmann (2) , Harley Kurata (3) , Shawn Lamothe (3) , Jasmine Maghera (3) , Rami Abou Jamra (4) , Anna Alkelai (5) , Stylianos Antonarakis (6) , Isis Atallah , Omer Bar-Yosef (7) , Frédéric Bilan (8, 9) , Kathrine Bjorgo , Xavier Blanc (10) , Patrick van Bogaert (9) , Yoav Bolkier (7) , Lindsay Burrage (11) , Björn Christ , Jorge Granadillo (12) , Patricia Dickson (12) , Kirsten Donald , Christèle Dubourg (13, 14) , Aviva Eliyahu (7) , Lisa Emrick , Kendra Engleman , Michaela Veronika Gonfiantini (15) , Jean-Marc Good (16) , Judith Kalser (16) , Chiara Kloeckner , Guus Lachmeijer , Marina Macchiaiolo (15) , Francesco Nicita , Sylvie Odent (17, 13) , Emily O’heir (1, 18) , Xilma Ortiz-Gonzalez (19) , Marta Pacio-Miguez (20) , María Palomares-Bralo (20) , Loren Pena , Konrad Platzer , Mathieu Quinodoz , Emmanuelle Ranza , Jill Rosenfeld , Eliane Roulet-Perez (16) , Avni Santani , Fernando Santos-Simarro (20) , Ben Pode-Shakked (7) , Cara Skraban , Rachel Slaugh (12) , Andrea Superti-Furga (16) , Isabelle Thiffault , Richard van Jaabrsveld , Marie Vincent (21, 22) , Hong-Gang Wang , Pia Zacher , Mercedes Alejandro , Mahshid Azamian , Carlos Bacino , Ashok Balasubramanyam , Hsiao-Tuan Chao , Gary Clark , William Craigen , Hongzheng Dai , Shweta Dhar , Alica Goldman , Neil Hanchard , Fariha Jamal , Lefkothea Karaviti , Seema Lalani , Brendan Lee , Richard Lewis , Ronit Marom , Paolo Moretti , David Murdock , Sarah Nicholas , James Orengo , Jennifer Posey , Lorraine Potocki , Susan Samson , Daryl Scott , Alyssa Tran , Tiphanie Vogel , Michael Wangler , Shinya Yamamoto , Christine Eng , Pengfei Liu , Patricia Ward , Edward Behrens , Matthew Deardorff , Marni Falk , Kelly Hassey , Kathleen Sullivan , Adeline Vanderver , David Goldstein , Heidi Cope , Allyn Mcconkie-Rosell , Kelly Schoch , Vandana Shashi (2) , Edward Smith , Jennifer Sullivan , Queenie K.-G. Tan , Nicole Walley , Pankaj Agrawal , Alan Beggs , Gerard Berry , Lauren Briere , Laurel Cobban , Matthew Coggins , Cynthia Cooper , Elizabeth Fieg , Frances High , Ingrid Holm , Susan Korrick , Joel Krier , Sharyn Lincoln , Joseph Loscalzo , Richard Maas , Calum Macrae , J. Carl Pallais , Deepak Rao , Edwin Silverman , Joan Stoler , David Sweetser , Melissa Walker , Chris Walsh , Cecilia Esteves , Emily Kelley , Isaac Kohane , Kimberly Leblanc , Alexa Mccray , Anna Nagy , Surendra Dasari , Brendan Lanpher , Ian Lanza , Eva Morava , Devin Oglesbee , Guney Bademci , Deborah Barbouth , Stephanie Bivona , Olveen Carrasquillo , Ta Chen Peter Chang , Irman Forghani , Alana Grajewski , Rosario Isasi , Byron Lam , Roy Levitt , Xue Zhong Liu , Jacob Mccauley , Ralph Sacco , Mario Saporta , Judy Schaechter , Mustafa Tekin , Fred Telischi , Willa Thorson , Stephan Zuchner , Heather Colley , Jyoti Dayal , David Eckstein , Laurie Findley , Donna Krasnewich , Laura Mamounas , Teri Manolio , John Mulvihill , Grace Lamoure , Madison Goldrich , Tiina Urv , Argenia Doss , Maria Acosta , Carsten Bonnenmann , Precilla D’souza , David Draper , Carlos Ferreira , Rena Godfrey , Catherine Groden , Ellen Macnamara , Valerie Maduro , Thomas Markello , Avi Nath , Donna Novacic , Barbara Pusey , Camilo Toro , Colleen Wahl , Eva Baker , Elizabeth Burke , David Adams , William Gahl , May Christine V. Malicdan , Cynthia Tifft , Lynne Wolfe , John Yang , Bradley Power , Bernadette Gochuico , Laryssa Huryn , Lea Latham , Joie Davis , Deborah Mosbrook-Davis , Francis Rossignol , Ben Solomon , John Macdowall , Audrey Thurm , Wadih Zein , Muhammad Yousef , Margaret Adam , Laura Amendola , Michael Bamshad , Anita Beck , Jimmy Bennett , Beverly Berg-Rood , Elizabeth Blue , Brenna Boyd , Peter Byers , Sirisak Chanprasert , Michael Cunningham , Katrina Dipple , Daniel Doherty , Dawn Earl , Ian Glass , Katie Golden-Grant , Sihoun Hahn , Anne Hing , Fuki Hisama , Martha Horike-Pyne , Gail Jarvik , Jeffrey Jarvik , Suman Jayadev , Christina Lam , Kenneth Maravilla , Heather Mefford , J. Lawrence Merritt , Ghayda Mirzaa , Deborah Nickerson , Wendy Raskind , Natalie Rosenwasser , C. Ron Scott , Angela Sun , Virginia Sybert , Stephanie Wallace , Mark Wener , Tara Wenger , Euan Ashley , Gill Bejerano , Jonathan Bernstein , Devon Bonner , Terra Coakley , Liliana Fernandez , Paul Fisher , Laure Fresard , Jason Hom , Yong Huang , Jennefer Kohler , Elijah Kravets , Marta Majcherska , Beth Martin , Shruti Marwaha , Colleen Mccormack , Archana Raja , Chloe Reuter , Maura Ruzhnikov , Jacinda Sampson , Kevin Smith , Shirley Sutton , Holly Tabor , Brianna Tucker , Matthew Wheeler , Diane Zastrow , Chunli Zhao , William Byrd , Andrew Crouse , Matthew Might , Mariko Nakano-Okuno , Jordan Whitlock , Gabrielle Brown , Manish Butte , Esteban Dell’angelica , Naghmeh Dorrani , Emilie Douine , Brent Fogel , Irma Gutierrez , Alden Huang , Deborah Krakow , Hane Lee , Sandra Loo , Bryan Mak , Martin Martin , Julian Martínez-Agosto , Elisabeth Mcgee , Stanley Nelson , Shirley Nieves-Rodriguez , Christina G.S. Palmer , Jeanette Papp , Neil Parker , Genecee Renteria , Rebecca Signer , Janet Sinsheimer , Jijun Wan , Lee-Kai Wang , Katherine Wesseling Perry , Jeremy Woods , Justin Alvey , Ashley Andrews , Jim Bale , John Bohnsack , Lorenzo Botto , John Carey , Laura Pace , Nicola Longo , Gabor Marth , Aaron Quinlan , Matt Velinder , Dave Viskochil , Pinar Bayrak-Toydemir , Rong Mao , Monte Westerfield , Anna Bican , Elly Brokamp , Laura Duncan , Rizwan Hamid , Jennifer Kennedy , Mary Kozuira , John Newman , John Phillipsiii , Lynette Rives , Amy Robertson , Emily Solem , Joy Cogan , F. Sessions Cole , Nichole Hayes , Dana Kiley , Kathy Sisco , Jennifer Wambach , Daniel Wegner , Dustin Baldridge , Stephen Pak , Timothy Schedl , Jimann Shin , Lilianna Solnica-Krezel , Eric Rush (23, 24, 25) , Geoffrey Pitt (26) , Ping Yee Billie Au (27)
Lance Rodan
Isis Atallah
  • Function : Author
Kathrine Bjorgo
  • Function : Author
Yoav Bolkier
  • Function : Author
Björn Christ
  • Function : Author
Kirsten Donald
  • Function : Author
Lisa Emrick
  • Function : Author
Kendra Engleman
  • Function : Author
Chiara Kloeckner
  • Function : Author
Guus Lachmeijer
  • Function : Author
Francesco Nicita
  • Function : Author
Loren Pena
  • Function : Author
Konrad Platzer
  • Function : Author
Mathieu Quinodoz
  • Function : Author
Emmanuelle Ranza
  • Function : Author
Jill Rosenfeld
Avni Santani
  • Function : Author
Cara Skraban
  • Function : Author
Isabelle Thiffault
Richard van Jaabrsveld
  • Function : Author
Hong-Gang Wang
  • Function : Author
Pia Zacher
  • Function : Author
Mercedes Alejandro
  • Function : Author
Mahshid Azamian
  • Function : Author
Carlos Bacino
  • Function : Author
Ashok Balasubramanyam
  • Function : Author
Hsiao-Tuan Chao
  • Function : Author
Gary Clark
  • Function : Author
William Craigen
  • Function : Author
Hongzheng Dai
  • Function : Author
Shweta Dhar
  • Function : Author
Alica Goldman
  • Function : Author
Neil Hanchard
Fariha Jamal
  • Function : Author
Lefkothea Karaviti
  • Function : Author
Seema Lalani
  • Function : Author
Brendan Lee
  • Function : Author
Richard Lewis
Ronit Marom
  • Function : Author
Paolo Moretti
  • Function : Author
David Murdock
  • Function : Author
Sarah Nicholas
  • Function : Author
James Orengo
  • Function : Author
Jennifer Posey
Lorraine Potocki
  • Function : Author
Susan Samson
  • Function : Author
Daryl Scott
  • Function : Author
Alyssa Tran
  • Function : Author
Tiphanie Vogel
  • Function : Author
Michael Wangler
  • Function : Author
Shinya Yamamoto
  • Function : Author
Christine Eng
  • Function : Author
Pengfei Liu
  • Function : Author
Patricia Ward
  • Function : Author
Edward Behrens
  • Function : Author
Matthew Deardorff
  • Function : Author
Marni Falk
  • Function : Author
Kelly Hassey
  • Function : Author
Kathleen Sullivan
  • Function : Author
Adeline Vanderver
  • Function : Author
David Goldstein
  • Function : Author
Heidi Cope
  • Function : Author
Allyn Mcconkie-Rosell
  • Function : Author
Kelly Schoch
  • Function : Author
Vandana Shashi
  • Function : Correspondent author
  • PersonId : 909391

Connectez-vous pour contacter l'auteur
Edward Smith
  • Function : Author
Jennifer Sullivan
  • Function : Author
Queenie K.-G. Tan
  • Function : Author
Nicole Walley
  • Function : Author
Pankaj Agrawal
  • Function : Author
Alan Beggs
  • Function : Author
Gerard Berry
  • Function : Author
Lauren Briere
  • Function : Author
Laurel Cobban
  • Function : Author
Matthew Coggins
  • Function : Author
Cynthia Cooper
  • Function : Author
Elizabeth Fieg
  • Function : Author
Frances High
  • Function : Author
Ingrid Holm
  • Function : Author
Susan Korrick
  • Function : Author
Joel Krier
  • Function : Author
Sharyn Lincoln
  • Function : Author
Joseph Loscalzo
  • Function : Author
Richard Maas
  • Function : Author
Calum Macrae
  • Function : Author
J. Carl Pallais
  • Function : Author
Deepak Rao
  • Function : Author
Edwin Silverman
Joan Stoler
  • Function : Author
David Sweetser
  • Function : Author
Melissa Walker
  • Function : Author
Chris Walsh
  • Function : Author
Cecilia Esteves
  • Function : Author
Emily Kelley
  • Function : Author
Isaac Kohane
Kimberly Leblanc
  • Function : Author
Alexa Mccray
  • Function : Author
Anna Nagy
  • Function : Author
Surendra Dasari
  • Function : Author
Brendan Lanpher
  • Function : Author
Ian Lanza
  • Function : Author
Eva Morava
  • Function : Author
Devin Oglesbee
  • Function : Author
Guney Bademci
  • Function : Author
Deborah Barbouth
  • Function : Author
Stephanie Bivona
  • Function : Author
Olveen Carrasquillo
  • Function : Author
Ta Chen Peter Chang
  • Function : Author
Irman Forghani
  • Function : Author
Alana Grajewski
  • Function : Author
Rosario Isasi
  • Function : Author
Byron Lam
  • Function : Author
Roy Levitt
  • Function : Author
Xue Zhong Liu
  • Function : Author
Jacob Mccauley
  • Function : Author
Ralph Sacco
  • Function : Author
Mario Saporta
  • Function : Author
Judy Schaechter
  • Function : Author
Mustafa Tekin
  • Function : Author
Fred Telischi
  • Function : Author
Willa Thorson
  • Function : Author
Stephan Zuchner
Heather Colley
  • Function : Author
Jyoti Dayal
  • Function : Author
David Eckstein
  • Function : Author
Laurie Findley
  • Function : Author
Donna Krasnewich
  • Function : Author
Laura Mamounas
  • Function : Author
Teri Manolio
  • Function : Author
John Mulvihill
  • Function : Author
Grace Lamoure
  • Function : Author
Madison Goldrich
  • Function : Author
Tiina Urv
  • Function : Author
Argenia Doss
  • Function : Author
Maria Acosta
  • Function : Author
Carsten Bonnenmann
  • Function : Author
Precilla D’souza
  • Function : Author
David Draper
  • Function : Author
Carlos Ferreira
Rena Godfrey
  • Function : Author
Catherine Groden
  • Function : Author
Ellen Macnamara
  • Function : Author
Valerie Maduro
  • Function : Author
Thomas Markello
  • Function : Author
Avi Nath
  • Function : Author
Donna Novacic
  • Function : Author
Barbara Pusey
  • Function : Author
Camilo Toro
  • Function : Author
Colleen Wahl
  • Function : Author
Eva Baker
  • Function : Author
Elizabeth Burke
  • Function : Author
David Adams
William Gahl
  • Function : Author
May Christine V. Malicdan
  • Function : Author
Cynthia Tifft
  • Function : Author
Lynne Wolfe
  • Function : Author
John Yang
  • Function : Author
Bradley Power
  • Function : Author
Bernadette Gochuico
  • Function : Author
Laryssa Huryn
  • Function : Author
Lea Latham
  • Function : Author
Joie Davis
  • Function : Author
Deborah Mosbrook-Davis
  • Function : Author
Francis Rossignol
  • Function : Author
Ben Solomon
  • Function : Author
John Macdowall
  • Function : Author
Audrey Thurm
  • Function : Author
Wadih Zein
  • Function : Author
Muhammad Yousef
  • Function : Author
Margaret Adam
  • Function : Author
Laura Amendola
  • Function : Author
Michael Bamshad
  • Function : Author
Anita Beck
  • Function : Author
Jimmy Bennett
  • Function : Author
Beverly Berg-Rood
  • Function : Author
Elizabeth Blue
  • Function : Author
Brenna Boyd
  • Function : Author
Peter Byers
  • Function : Author
Sirisak Chanprasert
  • Function : Author
Michael Cunningham
Katrina Dipple
  • Function : Author
Daniel Doherty
  • Function : Author
Dawn Earl
  • Function : Author
Ian Glass
  • Function : Author
Katie Golden-Grant
  • Function : Author
Sihoun Hahn
  • Function : Author
Anne Hing
  • Function : Author
Fuki Hisama
  • Function : Author
Martha Horike-Pyne
  • Function : Author
Gail Jarvik
  • Function : Author
Jeffrey Jarvik
  • Function : Author
Suman Jayadev
  • Function : Author
Christina Lam
  • Function : Author
Kenneth Maravilla
  • Function : Author
Heather Mefford
  • Function : Author
J. Lawrence Merritt
  • Function : Author
Ghayda Mirzaa
  • Function : Author
Deborah Nickerson
  • Function : Author
Wendy Raskind
  • Function : Author
Natalie Rosenwasser
  • Function : Author
C. Ron Scott
  • Function : Author
Angela Sun
  • Function : Author
Virginia Sybert
  • Function : Author
Stephanie Wallace
  • Function : Author
Mark Wener
  • Function : Author
Tara Wenger
  • Function : Author
Euan Ashley
  • Function : Author
Gill Bejerano
  • Function : Author
Jonathan Bernstein
Devon Bonner
  • Function : Author
Terra Coakley
  • Function : Author
Liliana Fernandez
  • Function : Author
Paul Fisher
  • Function : Author
Laure Fresard
  • Function : Author
Jason Hom
  • Function : Author
Yong Huang
  • Function : Author
Jennefer Kohler
  • Function : Author
Elijah Kravets
  • Function : Author
Marta Majcherska
  • Function : Author
Beth Martin
  • Function : Author
Shruti Marwaha
  • Function : Author
Colleen Mccormack
  • Function : Author
Archana Raja
  • Function : Author
Chloe Reuter
  • Function : Author
Maura Ruzhnikov
  • Function : Author
Jacinda Sampson
  • Function : Author
Kevin Smith
  • Function : Author
Shirley Sutton
  • Function : Author
Holly Tabor
  • Function : Author
Brianna Tucker
  • Function : Author
Matthew Wheeler
  • Function : Author
Diane Zastrow
  • Function : Author
Chunli Zhao
  • Function : Author
William Byrd
  • Function : Author
Andrew Crouse
  • Function : Author
Matthew Might
  • Function : Author
Mariko Nakano-Okuno
  • Function : Author
Jordan Whitlock
  • Function : Author
Gabrielle Brown
  • Function : Author
Manish Butte
  • Function : Author
Esteban Dell’angelica
  • Function : Author
Naghmeh Dorrani
  • Function : Author
Emilie Douine
  • Function : Author
Brent Fogel
  • Function : Author
Irma Gutierrez
  • Function : Author
Alden Huang
  • Function : Author
Deborah Krakow
  • Function : Author
Hane Lee
  • Function : Author
Sandra Loo
  • Function : Author
Bryan Mak
  • Function : Author
Martin Martin
  • Function : Author
Julian Martínez-Agosto
  • Function : Author
Elisabeth Mcgee
  • Function : Author
Stanley Nelson
  • Function : Author
Shirley Nieves-Rodriguez
  • Function : Author
Christina G.S. Palmer
  • Function : Author
Jeanette Papp
  • Function : Author
Neil Parker
  • Function : Author
Genecee Renteria
  • Function : Author
Rebecca Signer
  • Function : Author
Janet Sinsheimer
  • Function : Author
Jijun Wan
  • Function : Author
Lee-Kai Wang
  • Function : Author
Katherine Wesseling Perry
  • Function : Author
Jeremy Woods
  • Function : Author
Justin Alvey
  • Function : Author
Ashley Andrews
  • Function : Author
Jim Bale
  • Function : Author
John Bohnsack
  • Function : Author
Lorenzo Botto
  • Function : Author
John Carey
  • Function : Author
Laura Pace
  • Function : Author
Nicola Longo
  • Function : Author
Gabor Marth
  • Function : Author
Aaron Quinlan
  • Function : Author
Matt Velinder
  • Function : Author
Dave Viskochil
  • Function : Author
Pinar Bayrak-Toydemir
  • Function : Author
Rong Mao
  • Function : Author
Monte Westerfield
  • Function : Author
Anna Bican
  • Function : Author
Elly Brokamp
  • Function : Author
Laura Duncan
  • Function : Author
Rizwan Hamid
  • Function : Author
Jennifer Kennedy
  • Function : Author
Mary Kozuira
  • Function : Author
John Newman
  • Function : Author
John Phillipsiii
  • Function : Author
Lynette Rives
  • Function : Author
Amy Robertson
  • Function : Author
Emily Solem
  • Function : Author
Joy Cogan
  • Function : Author
F. Sessions Cole
  • Function : Author
Nichole Hayes
  • Function : Author
Dana Kiley
  • Function : Author
Kathy Sisco
  • Function : Author
Jennifer Wambach
  • Function : Author
Daniel Wegner
  • Function : Author
Dustin Baldridge
  • Function : Author
Stephen Pak
  • Function : Author
Timothy Schedl
  • Function : Author
Jimann Shin
  • Function : Author
Lilianna Solnica-Krezel
  • Function : Author

Abstract

Purpose: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.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results: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.Conclusion: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.

Domains

Genetics
Fichier principal
Vignette du fichier
Rodan et al - 2021 - Phenotypic expansion of CACNA1C-associated disorders_CACNA1C_GIM_Revisions_Clean_Final.pdf (2.36 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03519600 , version 1 (12-01-2022)

Identifiers

Cite

Lance Rodan, Rebecca Spillmann, Harley Kurata, Shawn Lamothe, Jasmine Maghera, et al.. Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations. Genetics in Medicine, 2021, 23 (10), pp.1922-1932. ⟨10.1038/s41436-021-01232-8⟩. ⟨hal-03519600⟩
217 View
253 Download

Altmetric

Share

Gmail Facebook X LinkedIn More