A loss-of-function CACNA1A mutation causing benign paroxysmal torticollis of infancy.
Benign paroxysmal torticollis of infancy (BPTI) is a rare paroxysmal disorder characterized by recurrent episodes of head tilt and accompanying general symptoms which remit spontaneously. The rare association with gain-of-function CACNA1A mutations, similar to hemiplegic migraine, has been reported. We report here two new BPTI patients from the same family carrying a heterozygous mutation in the CACNA1A gene leading to the change p.Glu533Lys. Functional analysis revealed that this mutation induces a loss of channel function due to impaired gating by voltage and much lower current density. Our data suggest that BPTI, a periodic syndrome commonly considered a migraine precursor, constitutes an age-specific manifestation of defective neuronal calcium channel activity.
Grup de Recerca en Neurologia Pediàtrica, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Marta
M
Vila-Pueyo
Laboratori de Fisiologia Molecular i Canalopaties, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Gemma G
GG
Gené
Secció de Neurologia Pediàtrica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Marina
M
Flotats-Bastardes
Laboratori de Fisiologia Molecular i Canalopaties, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Xabier
X
Elorza
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, Spain.
Cèlia
C
Sintas
Laboratori de Fisiologia Molecular i Canalopaties, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Miguel A
MA
Valverde
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, Spain.
Bru
B
Cormand
Laboratori de Fisiologia Molecular i Canalopaties, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
José M
JM
Fernández-Fernández
Grup de Recerca en Neurologia Pediàtrica, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; Secció de Neurologia Pediàtrica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Electronic address: amacaya@vhebron.net.
Alfons
A
Macaya
D015220:Calcium Channels / Q000235:genetics*; D002675:Child, Preschool; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D014103:Torticollis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
Benign paroxysmal torticollis of infancy; CACNA1A; Genetics; P/Q channel; Patch clamp