Miryam Carecchio1, Chiara Reale2, Federica Invernizzi2, Valentina Monti2, Simona Petrucci3, Monia Ginevrino4, Francesca Morgante5, Giovanna Zorzi6, Federica Zibordi6, Anna Rita Bentivoglio7, Enza Maria Valente4, Nardo Nardocci6, Barbara Garavaglia8. 1. Molecular Neurogenetics Unit, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy; Department of Child Neurology, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy; Department of Translational Medicine, University of Milan Bicocca, Milan, Italy. 2. Molecular Neurogenetics Unit, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy. 3. Department of Neurological Sciences, Sapienza University, Rome, Italy. 4. Department of Medicine and Surgery, University of Salerno, Salerno, Italy. 5. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 6. Department of Child Neurology, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy. 7. Institute of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy. 8. Molecular Neurogenetics Unit, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy. Electronic address: barbara.garavaglia@istituto-besta.it.
Abstract
BACKGROUND: Mutations in HPCA, a gene implicated in calcium signaling in the striatum, have been recently described in recessive dystonia cases previously grouped under the term "DYT2 dystonia". Positive patients reported so far show focal onset during childhood with subsequent generalization and a slowly progressive course to adulthood. METHODS: 73 patients with isolated dystonia of various distribution, manifesting within 21 years of age, were enrolled in this Italian study and underwent a mutational screening of HPCA gene by means of Sanger sequencing. RESULTS/ CONCLUSIONS: Mean age at onset was 10.2 (±5.1) years and mean age at the time of genetic testing was 33 (±14.2) years. Mean disease duration at the time of enrollment was 22.7 (±12.8) years. None of the patients enrolled was found to carry HPCA mutations, rising suspicion that these probably represent a very rare cause of dystonia in childhood-adolescence. Larger studies will help determining the real mutational frequency of this gene also in different ethnic groups.
BACKGROUND: Mutations in HPCA, a gene implicated in calcium signaling in the striatum, have been recently described in recessive dystonia cases previously grouped under the term "DYT2dystonia". Positive patients reported so far show focal onset during childhood with subsequent generalization and a slowly progressive course to adulthood. METHODS: 73 patients with isolated dystonia of various distribution, manifesting within 21 years of age, were enrolled in this Italian study and underwent a mutational screening of HPCA gene by means of Sanger sequencing. RESULTS/ CONCLUSIONS: Mean age at onset was 10.2 (±5.1) years and mean age at the time of genetic testing was 33 (±14.2) years. Mean disease duration at the time of enrollment was 22.7 (±12.8) years. None of the patients enrolled was found to carry HPCA mutations, rising suspicion that these probably represent a very rare cause of dystonia in childhood-adolescence. Larger studies will help determining the real mutational frequency of this gene also in different ethnic groups.