Abstract
Episodic ataxia is an autosomal dominant ion channel disorder characterized by paroxysmal attacks of incoordination. Episodic ataxia type 2 (EA2) is caused by mutations in CACNA1A. EA2 mutations are mostly nonsense and sometimes missense mutations. However, in some typical EA2 families, CACNA1A sequencing does not detect any point mutation. Herein, we have designed a quantitative multiplex polymerase chain reaction of short fluorescent fragment test to screen the 50 exons of CACNA1A and investigated 27 probands referred for molecular diagnosis of EA2 who did not show any point mutation in CACNA1A. We have identified four different exonic deletions in four patients with a typical EA2 phenotype. These results establish the need to complete sequencing analysis by a screening for deletions to ensure an accurate molecular diagnosis of EA2.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW (2007) Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain 130:2484–2493
Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM et al (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 87:543–552
Mori Y, Friedrich T, Kim MS, Mikami A, Nakai J, Ruth P et al (1991) Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature 350:398–402
Denier C, Ducros A, Vahedi K, Joutel A, Thierry P, Ritz A et al (1999) High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2. Neurology 52:1816–1821
Jen J, Kim GW, Baloh RW (2004) Clinical spectrum of episodic ataxia type 2. Neurology 62:17–22
Mantuano E, Veneziano L, Spadaro M, Giunti P, Guida S, Leggio MG et al (2004) Clusters of non-truncating mutations of P/Q type Ca2+ channel subunit Ca(v)2.1 causing episodic ataxia 2. J Med Genet 41:e82
Eunson LH, Graves TD, Hanna MG (2005) New calcium channel mutations predict aberrant RNA splicing in episodic ataxia. Neurology 65:308–310
Riant F, Mourtada R, Saugier-Veber P, Tournier-Lasserve E (2008) Large CACNA1A deletion in a family with episodic ataxia type 2. Arch Neurol 65:817–820
Casilli F, Di Rocco ZC, Gad S, Tournier I, Stoppa-Lyonnet D, Frebourg T et al (2002) Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments. Hum Mutat 20:218–226
Saugier-Veber P, Goldenberg A, Drouin-Garraud V, de La Rochebrochard C, Layet V, Drouot N et al (2006) Simple detection of genomic microdeletions and microduplications using QMPSF in patients with idiopathic mental retardation. Eur J Hum Genet 14:1009–1017
DeMaria CD, Soong TW, Alseikhan BA, Alvania RS, Yue DT (2001) Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels. Nature 411:484–489
Dunlap K (2007) Calcium channels are models of self-control. J Gen Physiol 129:379–383
Kolomietz E, Meyn MS, Pandita A, Squire JA (2002) The role of Alu repeat clusters as mediators of recurrent chromosomal aberrations in tumors. Genes Chromosomes Cancer 35:97–112
Deininger PL, Batzer MA (1999) Alu repeats and human disease. Mol Genet Metab 67:183–193
van Zelm MC, Geertsema C, Nieuwenhuis N, de Ridder D, Conley ME, Schiff C et al (2008) Gross deletions involving IGHM, BTK, or Artemis: a model for genomic lesions mediated by transposable elements. Am J Hum Genet 82:320–332
Kerber KA, Jen JC, Lee H, Nelson SF, Baloh RW (2007) A new episodic ataxia syndrome with linkage to chromosome 19q13. Arch Neurol 64:749–752
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Riant, F., Lescoat, C., Vahedi, K. et al. Identification of CACNA1A large deletions in four patients with episodic ataxia. Neurogenetics 11, 101–106 (2010). https://doi.org/10.1007/s10048-009-0208-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10048-009-0208-y