Abstract
Peroxisomal biogenesis disorders (PBDs) consist of a heterogeneous group of autosomal recessive diseases, in which peroxisome assembly and proliferation are impaired leading to severe multisystem disease and early death. PBDs include Zellweger spectrum disorders (ZSDs) with a relatively mild clinical phenotype caused by PEX1, (MIM# 602136), PEX2 (MIM# 170993), PEX6 (MIM# 601498), PEX10 (MIM# 602859), PEX12 (MIM# 601758), and PEX16 (MIM# 603360) mutations. Three adult patients are reported belonging to a non-consanguineous French family affected with slowly progressive cerebellar ataxia, axonal neuropathy, and pyramidal signs. Mental retardation and diabetes mellitus were optional. The age at onset was in childhood or in adolescence (3–15 years). Brain MRI showed marked cerebellar atrophy. Biochemical blood analyses suggested a mild peroxisomal defect. With whole exome sequencing, two mutations in PEX10 were found in the three patients: c.827G>T (novel) causing the missense change p.Cys276Phe and c.932G>A causing the missense change p.Arg311Gln. The phenotypic spectrum related to PEX10 mutations includes slowly progressive, syndromic recessive ataxia.
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Acknowledgments
We wish to acknowledge the help of Bernard Jost, Serge Vicaire, Stéphanie Legras, Michael Dumas, and Véronique Geoffroy for the next-generation sequencing and analysis.
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The final manuscript has been read and approved by all authors who accepted full responsibility for the design and undertaking of the original article, had access to the data and controlled the decision to publish.
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The study was approved by the local ethics committee.
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This study was supported by funds from the Agence Nationale pour la Recherche-Maladies Rares and Maladies Neurologiques et Psychiatriques (ANR-09-MNPS-001-01 to M.K.), the ANR/E-rare JTC 2011 “Euro-SCAR” (2011-RARE-004-01 to M.K.).
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Mathilde Renaud and Claire Guissart have equally contributed to this work.
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Renaud, M., Guissart, C., Mallaret, M. et al. Expanding the spectrum of PEX10-related peroxisomal biogenesis disorders: slowly progressive recessive ataxia. J Neurol 263, 1552–1558 (2016). https://doi.org/10.1007/s00415-016-8167-3
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DOI: https://doi.org/10.1007/s00415-016-8167-3