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 iPLA(2)-VIA (cytosolic Ca(2+)-independent phospholipids A(2), 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.