SCARB2 Mutations in Progressive Myoclonus Epilepsy (PME) Without Renal Failure

L. M DIBBENS; R MICHDUCCI; R WALLACE; A. G BASSUK; D. A POWER; C. A TASSINARI; E ANDERMANN; A. E LEHESJOKI; S. F BERKOVIC; A GAMBARDELLA; F ANDERMANN; G RUBBOLI; M. A BAYLY; T JOENSUU; D. F VEARS; S FRANCESCHETTI; L CANAFOGLIA

doi:10.1002/ana.21765

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SCARB2 Mutations in Progressive Myoclonus Epilepsy (PME) Without Renal Failure

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SCARB2 Mutations in Progressive Myoclonus Epilepsy (PME) Without Renal Failure

L. M DIBBENS, R MICHDUCCI, R WALLACE, A. G BASSUK, D. A POWER, C. A TASSINARI, E ANDERMANN, A. E LEHESJOKI, S. F BERKOVIC, A GAMBARDELLA, …

Annals of neurology, Vol.66(4), pp.532-536

2009

DOI: 10.1002/ana.21765

PMID: 19847901

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Abstract

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.

Neurology

Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy

Biological and medical sciences

Medical sciences

Nervous system (semeiology, syndromes)

Details

Title: Subtitle: SCARB2 Mutations in Progressive Myoclonus Epilepsy (PME) Without Renal Failure
Creators: L. M DIBBENS - SA Pathology, Women's and Children's Hospital, North Adelaide, Australia
R MICHDUCCI - Neurology Unit, Department of Neurosciences, Bellaria Hospital, Bologna, Italy
R WALLACE - Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia
A. G BASSUK - Department of Pediatrics, University of Iowa, Iowa City, IA, United States
D. A POWER - Department of Nephrology, Austin Health, Heidelberg, Victoria, Australia
C. A TASSINARI - Department of Neurological Sciences, University of Bologna, Bologna, Italy
E ANDERMANN - Neurogenetics Unit, Montreal Neurological Hospital and Institute, Montreal, Quebec, Canada
A. E LEHESJOKI - Polkhälsan Institute of Genetics, Department of Medical Genetics and Neuroscience Center, University of Helsinki, Finland
S. F BERKOVIC - Epilepsy Research Centre, Department of Medicine (Neurology), University of Melbourne, Austin Health, Heidelberg West, Australia
A GAMBARDELLA - Institute of Neurological Sciences, National Research Council, Mangone, Cosenza (CS), Italy
F ANDERMANN - Epilepsy Service, Montreal Neurological Hospital and Institute, Montreal, Quebec, Canada
G RUBBOLI - Neurology Unit, Department of Neurosciences, Bellaria Hospital, Bologna, Italy
M. A BAYLY - SA Pathology, Women's and Children's Hospital, North Adelaide, Australia
T JOENSUU - Polkhälsan Institute of Genetics, Department of Medical Genetics and Neuroscience Center, University of Helsinki, Finland
D. F VEARS - Epilepsy Research Centre, Department of Medicine (Neurology), University of Melbourne, Austin Health, Heidelberg West, Australia
S FRANCESCHETTI - Unit of Neurophysiopathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation, C. Besta Neurological Institute, Milan, Italy
L CANAFOGLIA - Unit of Neurophysiopathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation, C. Besta Neurological Institute, Milan, Italy
Resource Type: Journal article
Publication Details: Annals of neurology, Vol.66(4), pp.532-536
DOI: 10.1002/ana.21765
PMID: 19847901
NLM abbreviation: Ann Neurol
ISSN: 0364-5134
eISSN: 1531-8249
Publisher: Wiley-Liss; Hoboken, NJ
Language: English
Date published: 2009
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020600602771

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