Hallervorden-Spatz综合征的临床、磁共振成像特征及泛酸激酶2基因的突变检测

Clinical, magnetic resonance image features and detection of pantothenate kinase 2 gene mutations in Chinese patients with Hallervorden-Spatz syndrome

目的 研究中国人Hallervorden Spatz综合征的临床、磁共振成像 (MRI)特征与泛酸激酶 2(PANK2)基因的突变检测。方法 对 5例Hallervorden Spatz综合征患者的临床与脑MRI特征进行分析;应用聚合酶链反应(PCR)、DNA直接测序、聚合酶链反应 单链构象多态性和PCR产物酶切等技术检测 5例患者、3名家系成员及 51名健康人PANK2基因的碱基序列。结果 5例患者主要表现为锥体外系症状;头部MRIT2 加权像表现双侧苍白球、黑质等部位对称性低信号,其中 1例在苍白球低信号区的前内侧出现高信号,即“虎眼征”;检测出PANK2基因一个新的复合杂合突变:位于第三外显子 803位的A→G和第五外显子 1172位的T→A,导致所编码的氨基酸发生改变(分别为D268G和I391N)。结论 根据临床和头部MRI特征可临床诊断Hallervorden Spatz综合征,中国人Hallervorden Spatz综合征患者存在PANK2基因突变,具有PANK2基因突变的患者头部MRI表现有“虎眼征”。

Objective To study the clinical, magnetic resonance image(MRI) features and pantothenate kinase 2(PANK2) gene mutation of Chinese patients with Hallervorden-Spatz syndrome (HSS). Methods Five patients with a diagnosis of HSS were assessed according to their clinical and brain MRI features. PANK2 gene mutations were detected using polymerase chain reaction(PCR) , DNA sequence analysis, PCR- single strand conformation polymorphism and restriction enzyme digestion in 5 patients, 3 unaffected family members and 51 unrelated healthy persons.Results The main symptoms of 5 patients with HSS were extrapyramidal syndromes.T 2-weighted MRI scans showed a marked low signal intensity localized to bilateral globus pallidus and substantia nigra, and in one patient, presenting bilateral hyperintense signal within a hypointense region in the medial globus pallidus ,the “eye-of-the-tiger” sign. Novel compound heterozygous PANK2 gene mutations, A803G and T1172A, were found in one patient, leading to substitution of an aspartic for glycine codon at amino acid 268 (D268G) and an isoleucine for asparagine codon at amino acid 391 (I391N), respectively.Conclusions HSS can be diagnosed on the basis of clinical and brain MRI. PANK2 gene mutations might cause Hallervorden-Spatz syndrome in Chinese patients.And in patients with PANK2 gene mutation,T 2-weighted MRI of brain might show the “eye-of-the-tiger” sign.