OBJECTIVE: Mutations in SCARB2 were recently described as causing action myoclonus renal failure syndrome (AMRF). We hypothesized that mutations in SCARB2 might account for unsolved cases of progressive myoclonus epilepsy (PME) without renal impairment, especially those resembling Unverricht-Lundborg disease (ULD). Additionally, we searched for mutations in the PRICKLE1 gene, newly recognized as a cause of PME mimicking ULD. METHODS: We reviewed cases of PME referred for diagnosis over two decades in which a molecular diagnosis had not been reached. Patients were classified according to age of onset, clinical pattern, and associated neurological signs into "ULD-like" and "not ULD-like." After exclusion of mutations in cystatin B (CSTB), DNA was examined for sequence variation in SCARB2 and PRICKLE1. RESULTS: Of 71 cases evaluated, 41 were "ULD-like" and five had SCARB2 mutations. None of 30 "not ULD-like" cases were positive. The five patients with SCARB2 mutations had onset between 14 and 26 years of age, with no evidence of renal failure during 5.5 to 15 years of follow-up; four were followed until death. One living patient had slight proteinuria. A subset of 25 cases were sequenced for PRICKLE1 and no mutations were found. INTERPRETATION: Mutations in SCARB2 are an important cause of hitherto unsolved cases of PME resembling ULD at onset. SCARB2 should be evaluated even in the absence of renal involvement. Onset is in teenage or young adult life. Molecular diagnosis is important for counseling the patient and family, particularly as the prognosis is worse than classical ULD.
OBJECTIVE: Mutations in SCARB2 were recently described as causing action myoclonus renal failure syndrome (AMRF). We hypothesized that mutations in SCARB2 might account for unsolved cases of progressive myoclonus epilepsy (PME) without renal impairment, especially those resembling Unverricht-Lundborg disease (ULD). Additionally, we searched for mutations in the PRICKLE1 gene, newly recognized as a cause of PME mimicking ULD. METHODS: We reviewed cases of PME referred for diagnosis over two decades in which a molecular diagnosis had not been reached. Patients were classified according to age of onset, clinical pattern, and associated neurological signs into "ULD-like" and "not ULD-like." After exclusion of mutations in cystatin B (CSTB), DNA was examined for sequence variation in SCARB2 and PRICKLE1. RESULTS: Of 71 cases evaluated, 41 were "ULD-like" and five had SCARB2 mutations. None of 30 "not ULD-like" cases were positive. The five patients with SCARB2 mutations had onset between 14 and 26 years of age, with no evidence of renal failure during 5.5 to 15 years of follow-up; four were followed until death. One living patient had slight proteinuria. A subset of 25 cases were sequenced for PRICKLE1 and no mutations were found. INTERPRETATION: Mutations in SCARB2 are an important cause of hitherto unsolved cases of PME resembling ULD at onset. SCARB2 should be evaluated even in the absence of renal involvement. Onset is in teenage or young adult life. Molecular diagnosis is important for counseling the patient and family, particularly as the prognosis is worse than classical ULD.
Authors: Michelle Rothaug; Friederike Zunke; Joseph R Mazzulli; Michaela Schweizer; Hermann Altmeppen; Renate Lüllmann-Rauch; Wouter W Kallemeijn; Paulo Gaspar; Johannes M Aerts; Markus Glatzel; Paul Saftig; Dimitri Krainc; Michael Schwake; Judith Blanz Journal: Proc Natl Acad Sci U S A Date: 2014-10-14 Impact factor: 11.205
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: Silvana Franceschetti; Roberto Michelucci; Laura Canafoglia; Pasquale Striano; Antonio Gambardella; Adriana Magaudda; Paolo Tinuper; Angela La Neve; Edoardo Ferlazzo; Giuseppe Gobbi; Anna Teresa Giallonardo; Giuseppe Capovilla; Elisa Visani; Ferruccio Panzica; Giuliano Avanzini; Carlo Alberto Tassinari; Amedeo Bianchi; Federico Zara Journal: Neurology Date: 2014-01-02 Impact factor: 9.910
Authors: Mark A Corbett; Michael Schwake; Melanie Bahlo; Leanne M Dibbens; Meng Lin; Luke C Gandolfo; Danya F Vears; John D O'Sullivan; Thomas Robertson; Marta A Bayly; Alison E Gardner; Annemarie M Vlaar; G Christoph Korenke; Bastiaan R Bloem; Irenaeus F de Coo; Judith M A Verhagen; Anna-Elina Lehesjoki; Jozef Gecz; Samuel F Berkovic Journal: Am J Hum Genet Date: 2011-05-05 Impact factor: 11.025
Authors: Julie Turnbull; Jean-Marie Girard; Hannes Lohi; Elayne M Chan; Peixiang Wang; Erica Tiberia; Salah Omer; Mushtaq Ahmed; Christopher Bennett; Aruna Chakrabarty; Atul Tyagi; Yan Liu; Nela Pencea; XiaoChu Zhao; Stephen W Scherer; Cameron A Ackerley; Berge A Minassian Journal: Brain Date: 2012-09 Impact factor: 13.501