Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation
Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation
复制标题
DOI：
10.1002/ana.20771
复制
发表时间：
2006-02-01
影响因子：
11.2
通讯作者：
Meitinger, T
中科院分区：
文献类型：
--
作者：
Hartig, MB;Hörtnagel, K;Meitinger, T
目的：神经退行性变伴脑铁蓄积(NBIA)是一组以基底节核磁共振成像(MRI)改变为特征的疾病。在这些患者中，已经发现了编码线粒体泛酸激酶(PANK2)的基因的错义和无义突变。方法：研究方法。我们根据临床表现和放射成像完成了72名诊断为NBIA的患者的突变筛查。对PANK2基因的整个编码区(20p12.3)进行了点突变和缺失检测。结果：我们在48名患者中发现了这两个突变等位基因。缺失占突变等位基因的4%。有两个功能丧失等位基因的患者(n=11)总是在生命早期表现出症状。在存在错义突变的情况下(n=37)，发病年龄与泛酸酸激酶的残留活性相关。通过丧失行走能力来衡量疾病的进展在两组中都是不同的。我们没有观察到虎眼征和PANK2突变之间的严格相关性。在24例患者中，未发现PANK2突变。PANK2的解释缺失筛查应作为诊断谱的一部分。决定病程的因素不是酶的残存活性。有强有力的论据支持基因座异质性。
Objective: Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterized by magnetic resonance imaging (MRI) changes in basal ganglia. Both missense and nonsense mutations have been found in such patients in a gene encoding the mitochondrial pantothenate kinase (PANK2). Methods. We completed a mutation screen in 72 patients with the diagnosis NBIA based on clinical findings and radiological imaging. The entire coding region of the PANK2 gene (20p12.3) was investigated for point mutations and deletions. Results: We uncovered both mutant alleles in 48 patients. Deletions accounted for 4% of mutated alleles. Patients with two loss-of-function alleles (n = 11) displayed symptoms always at an early stage of life. In the presence of missense mutations (n = 37), the age of onset correlated with residual activity of the pantothenate kinase. Progression of disease measured by loss of ambulation was variable in both groups. We did not observe a strict correlation between the eye-of-the-tiger sign and PANK2 mutations. In 24 patients, no PANK2 mutation was identified. Interpretation Deletion screening of PANK2 should be part of the diagnostic spectrum. Factors other than enzymatic residual activity are determining the course of disease. There are strong arguments in favor of locus heterogeneity.