Clinical features of infantile neuroaxonal dystrophy and PLA2G6 gene testing
LU Yao, LIU Chun-Hua, WANG Yang
Department of Neonatology, Xianning Central Hospital/First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei 437100, China
Abstract Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease. Two boys aged 3 years and 4 years and 2 months respectively, were admitted to the hospital due to delayed mental and motor development. There were no abnormalities at birth, and both children had low muscle strength and tension on admission. One child was not able to stand alone and had impaired vision. Electromyography showed neurogenic damage, and head MRI revealed cerebellar atrophy. High-throughput sequencing revealed compound heterozygous mutations in the PLA2G6 gene in the two children. The mutations (IVS11-1G > T and c.1984C > G) in one child were new mutations, and immunohistochemistry showed a reduction in the protein expression of PLAG6 in the muscular tissue of this child. INAD has the main clinical manifestations of psychomotor developmental regression and cerebellar atrophy. High-throughput sequencing can help with clinical diagnosis.
Iodice A, Spagnoli C, Salerno GG, et al. Infantile neuroaxonal dystrophy and PLA2G6-associated neurodegeneration:an update for the diagnosis[J]. Brain Dev, 2017, 39(2):93-100.
[2]
Elsayed LEO, Mohammed IN, Hamed AAA, et al. Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family[J]. BMC Med Genet, 2018, 19(1):72.
[3]
Mascalchi M, Mari F, Berti B, et al. Fast progression of cerebellar atrophy in PLA2G6-associated infantile neuronal axonal dystrophy[J]. Cerebellum, 2017, 16(3):742-745.
[4]
Morgan NV, Westaway SK, Morton JE, et al. PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron[J]. Nat Genet, 2006, 38(7):752-754.
[5]
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424.
Ozes B, Karagoz N, Schüle R, et al. PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia[J]. Clin Genet, 2017, 92(5):534-539.
Nardocci N, Zorzi G, Farina L, et al. Infantile neuroaxonal dystrophy:clinical spectrum and diagnostic criteria[J]. Neurology, 1999, 52(7):1472-1478.
[10]
Polster B, Crosier M, Lindsay S, et al. Expression of PLA2G6 in human fetal development:implications for infantile neuroaxonal dystrophy[J]. Brain Res Bull, 2010, 83(6):374-379.
[11]
Ramanadham S, Ali T, Ashley JW, et al. Calcium-independent phospholipases A2 and their roles in biological processes and diseases[J]. J Lipid Res, 2015, 56(9):1643-1668.
[12]
Kapoor S, Shah MH, Singh N, et al. Genetic analysis of PLA2G6 in 22 Indian families with infantile neuroaxonal dystrophy, atypical late-onset neuroaxonal dystrophy and dystonia parkinsonism complex[J]. PLoS One, 2016, 11(5):e0155605.
[13]
Zhang P, Gao Z, Jiang Y, et al. Follow-up study of 25 Chinese children with PLA2G6-associated neurodegeneration[J]. Eur J Neurol, 2013, 20(2):322-330.
