Wu Y, Jiang Y, Gao Z, Wang J, Yuan Y, Xiong H, Chang X, Bao X, Zhang Y, Xiao J, Wu X
Department of Pediatrics, Peking University, First Hospital, Beijing, China.
Eur J Neurol. 2009 Feb;16(2):240-5. doi: 10.1111/j.1468-1331.2008.02397.x. Epub 2008 Dec 9.
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.
For 10 cases of INAD, extensive clinical investigations, neuropathological examination, and mutation screening in PLA2G6 were performed.
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.
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.
婴儿神经轴索性营养不良（INAD）是一种罕见的常染色体隐性神经退行性疾病。该疾病最典型的神经病理学发现是轴突肿胀。在2006年发现编码iPLA(2)-VIA（胞质钙非依赖性磷脂A(2)，第VIA组）的PLA2G6相关突变之前，神经病理学证据对明确诊断至关重要。全球仅发表了五项关于INAD患者的遗传学研究，共报道了44种突变。为明确中国INAD患者的临床和遗传特征，对10例患者进行了分析。
对10例INAD患者进行了全面的临床检查、神经病理学检查及PLA2G6突变筛查。
所有病例均表现出典型的临床特征。3例患者的皮肤或腓肠神经活检标本中发现轴突肿胀。共鉴定出12种PLA2G6突变，其中9种为新突变。这些新突变包括6种错义突变、1种使正常起始密码子缺失的突变、1种无义突变和1种剪接位点突变。
本研究鉴定出的9种新突变表明中国患者中PLA2G6突变谱具有独特性，并极大地扩展了INAD患者已知突变的范围。除病理证据外，基因分析可为INAD的明确诊断提供依据。
