Clinical study and PLA2G6 mutation screening analysis in Chinese patients with infantile neuroaxonal dystrophy
- 14 January 2009
- journal article
- Published by Wiley in European Journal of Neurology
- Vol. 16 (2), 240-245
- https://doi.org/10.1111/j.1468-1331.2008.02397.x
Abstract
Background and purpose: Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disorder. The most typical neuropathological finding of this disease is axonal swelling. Before the identification of associated mutations in PLA2G6‐encoding iPLA2‐VIA (cytosolic Ca2+‐independent phospholipids A2, group VIA) in 2006, neuropathological evidence was critical for definitive diagnosis. Only five genetic studies in INAD patients have been published worldwide, wherein 44 mutations were reported. To define the clinical and genetic characteristics of Chinese patients with INAD, 10 cases were analyzed. Methods: For 10 cases of INAD, extensive clinical investigations, neuropathological examination, and mutation screening in PLA2G6 were performed. Results: All cases displayed typical clinical features. Axonal swelling was found in skin or sural nerve biopsy specimens in three cases. Twelve PLA2G6 mutations were identified, nine of which were novel. These novel mutations include six missense, one abolishing the normal start codon, one nonsense, and one splice‐site mutation. Conclusions: The nine novel mutations identified in this study suggest the uniqueness of the PLA2G6 mutation spectrum in Chinese patients, and greatly extends the spectrum of known mutations in INAD patients. In addition to pathological evidence, genetic analysis can inform definitive diagnosis of INAD.Keywords
This publication has 14 references indexed in Scilit:
- Infantile neuroaxonal dystrophy: What's most important for the diagnosis?European Journal of Paediatric Neurology, 2008
- Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN)Neurology, 2008
- Disrupted Membrane Homeostasis and Accumulation of Ubiquitinated Proteins in a Mouse Model of Infantile Neuroaxonal Dystrophy Caused by PLA2G6 MutationsThe American Journal of Pathology, 2008
- Cerebellar atrophy without cerebellar cortex hyperintensity in infantile neuroaxonal dystrophy (INAD) due to PLA2G6 mutationEuropean Journal of Paediatric Neurology, 2007
- Calcium-independent phospholipase A2 and apoptosisBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2006
- PLA2G6 Mutation Underlies Infantile Neuroaxonal DystrophyAmerican Journal of Human Genetics, 2006
- PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain ironNature Genetics, 2006
- Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cellsCellular Signalling, 2005
- Infantile neuroaxonal dystrophy (Seitelberger's disease)Developmental Medicine and Child Neurology, 2002
- Pantothenate kinase-associated neurodegeneration (Hallervorden–Spatz syndrome)European Journal of Paediatric Neurology, 2002