Laura Canafoglia1, Angela Robbiano1, Davide Pareyson1, Ferruccio Panzica1, Lorenzo Nanetti1, Anna Rita Giovagnoli1, Anna Venerando1, Cinzia Gellera1, Silvana Franceschetti2, Federico Zara1. 1. From the Department of Neurophysiopathology and Epilepsy Centre (L.C., F.P., S.F.), Department of Neurology (D.P., L.N.), Laboratory of Cognitive Neurology and Rehabilitation, Neurology and Neuropathology Unit (A.R.G.), and Biochemistry and Genetics Department (A.V., C.G.), IRCCS Foundation C. Besta Neurological Institute, Milan; and Laboratory of Neurogenetics (A.R., F.Z.), Department of Neuroscience, Institute G. Gaslini, Genoa, Italy. 2. From the Department of Neurophysiopathology and Epilepsy Centre (L.C., F.P., S.F.), Department of Neurology (D.P., L.N.), Laboratory of Cognitive Neurology and Rehabilitation, Neurology and Neuropathology Unit (A.R.G.), and Biochemistry and Genetics Department (A.V., C.G.), IRCCS Foundation C. Besta Neurological Institute, Milan; and Laboratory of Neurogenetics (A.R., F.Z.), Department of Neuroscience, Institute G. Gaslini, Genoa, Italy. franceschetti@istituto-besta.it.
Abstract
OBJECTIVE: To identify the genetic cause of a familial form of late-onset action myoclonus in 2 unrelated patients. Both probands had 2 siblings displaying a similar disorder. Extensive laboratory examinations, including biochemical assessment for urine sialic acid in the 2 probands, were negative. METHODS: Exome sequencing was performed in the probands using an Illumina platform. Segregation analysis of putative mutations was performed in all family members by standard Sanger sequencing protocols. RESULTS: NEU1 mutations were detected in 3 siblings of each family with prominent cortical myoclonus presenting in the third decade of life and having a mild and slowly progressive course. They did not have macular cherry-red spot and their urinary sialic acid excretion was within normal values. Genetic analysis demonstrated a homozygous mutation in family 1 (c.200G>T, p.S67I) and 2 compound heterozygous mutations in family 2 (c.679G>A, p.G227R; c.913C>T, p.R305C). CONCLUSIONS: Our observation indicates that sialidosis should be suspected and the NEU1 gene analyzed in patients with isolated action myoclonus presenting in adulthood in the absence of other typical clinical and laboratory findings.
OBJECTIVE: To identify the genetic cause of a familial form of late-onset action myoclonus in 2 unrelated patients. Both probands had 2 siblings displaying a similar disorder. Extensive laboratory examinations, including biochemical assessment for urine sialic acid in the 2 probands, were negative. METHODS: Exome sequencing was performed in the probands using an Illumina platform. Segregation analysis of putative mutations was performed in all family members by standard Sanger sequencing protocols. RESULTS:NEU1 mutations were detected in 3 siblings of each family with prominent cortical myoclonus presenting in the third decade of life and having a mild and slowly progressive course. They did not have macular cherry-red spot and their urinary sialic acid excretion was within normal values. Genetic analysis demonstrated a homozygous mutation in family 1 (c.200G>T, p.S67I) and 2 compound heterozygous mutations in family 2 (c.679G>A, p.G227R; c.913C>T, p.R305C). CONCLUSIONS: Our observation indicates that sialidosis should be suspected and the NEU1 gene analyzed in patients with isolated action myoclonus presenting in adulthood in the absence of other typical clinical and laboratory findings.
Authors: Carolina Courage; Karen L Oliver; Eon Joo Park; Jillian M Cameron; Kariona A Grabińska; Mikko Muona; Laura Canafoglia; Antonio Gambardella; Edith Said; Zaid Afawi; Betul Baykan; Christian Brandt; Carlo di Bonaventura; Hui Bein Chew; Chiara Criscuolo; Leanne M Dibbens; Barbara Castellotti; Patrizia Riguzzi; Angelo Labate; Alessandro Filla; Anna T Giallonardo; Geza Berecki; Christopher B Jackson; Tarja Joensuu; John A Damiano; Sara Kivity; Amos Korczyn; Aarno Palotie; Pasquale Striano; Davide Uccellini; Loretta Giuliano; Eva Andermann; Ingrid E Scheffer; Roberto Michelucci; Melanie Bahlo; Silvana Franceschetti; William C Sessa; Samuel F Berkovic; Anna-Elina Lehesjoki Journal: Am J Hum Genet Date: 2021-04-01 Impact factor: 11.025
Authors: Mikko Muona; Samuel F Berkovic; Leanne M Dibbens; Karen L Oliver; Snezana Maljevic; Marta A Bayly; Tarja Joensuu; Laura Canafoglia; Silvana Franceschetti; Roberto Michelucci; Salla Markkinen; Sarah E Heron; Michael S Hildebrand; Eva Andermann; Frederick Andermann; Antonio Gambardella; Paolo Tinuper; Laura Licchetta; Ingrid E Scheffer; Chiara Criscuolo; Alessandro Filla; Edoardo Ferlazzo; Jamil Ahmad; Adeel Ahmad; Betul Baykan; Edith Said; Meral Topcu; Patrizia Riguzzi; Mary D King; Cigdem Ozkara; Danielle M Andrade; Bernt A Engelsen; Arielle Crespel; Matthias Lindenau; Ebba Lohmann; Veronica Saletti; João Massano; Michael Privitera; Alberto J Espay; Birgit Kauffmann; Michael Duchowny; Rikke S Møller; Rachel Straussberg; Zaid Afawi; Bruria Ben-Zeev; Kaitlin E Samocha; Mark J Daly; Steven Petrou; Holger Lerche; Aarno Palotie; Anna-Elina Lehesjoki Journal: Nat Genet Date: 2014-11-17 Impact factor: 38.330
Authors: Imre F Schene; Viera Kalinina Ayuso; Monique de Sain-van der Velden; Koen L I van Gassen; Inge Cuppen; Peter M van Hasselt; Gepke Visser Journal: JIMD Rep Date: 2015-07-05
Authors: Rodi Zutt; Martje E van Egmond; Jan Willem Elting; Peter Jan van Laar; Oebele F Brouwer; Deborah A Sival; Hubertus P Kremer; Tom J de Koning; Marina A Tijssen Journal: Nat Rev Neurol Date: 2015-11-10 Impact factor: 42.937