title: Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2).
abstract: Ataxia is a symptom that is often associated with syndromic inherited diseases. We previously reported the linkage of a novel syndrome, ataxia with blindness and deafness (SCAR3/SCABD, OMIM# 271250), to chromosome 6p21-p23 by linkage mapping of an Arab Israeli consanguineous family. We have now identified by whole-exome sequencing a homozygous missense mutation in the Arab Israeli family in the SLC52A2 gene located in 8qter, therefore excluding linkage of this family to 6p. We confirmed the involvement of SLC52A2 by the identification of a second mutation in an independent family with an identical syndromic presentation, which we suggest to name SCABD2. SCABD2 is therefore allelic to Brown-Vialleto-Van Laere syndrome type 2 defined by prominent motoneuronopathy and deafness, and also caused by SLC52A2 mutations. In the course of this project, we identified a clinically similar family with a homozygous missense mutation in PEX6, which is located in 6p21. Therefore, despite false linkage in the initial family, SCABD1/SCAR3 is located in 6p21 and is caused by PEX6 mutations. Both SLC52A2 and PEX6 should be included in screening panels for the diagnosis of syndromic inherited ataxias, particularly as patients with mutations in SLC52A2 can be ameliorated by riboflavin supplementation.
authors.affiliation: Equipe d'Accueil 7402, Institut Universitaire de Recherche Clinique, Université de Montpellier, Montpellier, France.|Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.
authors.forename: Claire
authors.identifier: 0000-0002-3944-5715
authors.initials: C
authors.lastname: Guissart
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Drouot
authors.affiliation: Department of Pediatrics, Hacettepe University, Ankara, Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Oncel
authors.affiliation: CHU de Nancy Pôle Enfants Service de Médecine Infantile et Génétique Clinique, Centre de Référence Syndrome Malformatif et Anomalies du Développement, Vandoeuvre, France.|Université de Lorraine Faculté de Médecine, Vandoeuvre, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.affiliation: Rambam Medical Center, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Barush
authors.affiliation: Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Laboratoire de Génétique médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine FMTS, Université de Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.identifier: 0000-0002-7682-559X
authors.initials: J
authors.lastname: Muller
authors.affiliation: Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: Ferdinandusse
authors.affiliation: Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Larrieu
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France.|CHU de Strasbourg-Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Anheim
authors.affiliation: Department of Pediatrics, Hacettepe University, Ankara, Turkey.
authors.forename: Elif Acar
authors.initials: EA
authors.lastname: Arslan
authors.affiliation: Equipe d'Accueil 7402, Institut Universitaire de Recherche Clinique, Université de Montpellier, Montpellier, France.|Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France.|CHU de Strasbourg-Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.affiliation: Department of Pediatrics, Hacettepe University, Ankara, Turkey.
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.affiliation: Equipe d'Accueil 7402, Institut Universitaire de Recherche Clinique, Université de Montpellier, Montpellier, France.|Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001766:Blindness / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D003638:Deafness / Q000175:diagnosis / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics*
chemical_list: D043562:Receptors, G-Protein-Coupled; C540350:SLC52A2 protein, human; C120153:WASF3 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C490759:PEX6 protein, human