Department of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland.
Eur J Neurol. 2010 Nov;17(11):1393-5. doi: 10.1111/j.1468-1331.2010.03028.x.
Frontotemporal lobar degeneration (FTLD) is a genetically complex disorder. The majority of mutations linked to FTLD families are found in the microtubule-associated protein tau (MAPT) and progranulin (PGRN) genes. Mutations in the chromatin-modifying protein 2B gene (CHMP2B) have been identified in a few families. However, CHMP2B has been showed to be a rare cause of FTLD. Our aim was to determine the frequency of CHMP2B mutations in a clinical series of patients with FTLD in Northern Finland.
We examined 72 (36 men) Finnish patients with FTLD. The mean age at onset was 58.9 (range 43–80). Symptoms of motor neuron disease (FTLDMND) were present in 12 patients (17%). Positive family history was detected in 28% of the patients. Mutations in MAPT and PGRN were excluded from these patients. All exons and exon–intron boundaries of the CHMP2B gene were sequenced.
No pathogenic CHMP2B mutations were found. A rare polymorphism in the non-coding region of exon 1 (rs36098294) and three other previously reported polymorphisms were detected.
Our results confirm that mutations in CHMP2B are not a common cause of FTLD. MAPT and PGRN mutations are also rare in Finnish population, suggesting that other, still unknown genetic factors may play a role in the pathogenesis of FTLD in Finnish population.
额颞叶变性（FTLD）是一种遗传复杂的疾病。大多数与 FTLD 家族相关的突变存在于微管相关蛋白 tau（MAPT）和颗粒蛋白前体（PGRN）基因中。在少数家族中已发现染色质修饰蛋白 2B 基因（CHMP2B）的突变。然而，CHMP2B 被认为是 FTLD 的罕见原因。我们的目的是确定 CHMP2B 突变在芬兰北部 FTLD 临床系列患者中的频率。
我们检查了 72 名（36 名男性）芬兰 FTLD 患者。发病年龄的平均值为 58.9 岁（范围 43-80 岁）。12 名患者（17％）存在运动神经元病（FTLDMND）的症状。28％的患者有阳性家族史。这些患者排除了 MAPT 和 PGRN 的突变。对 CHMP2B 基因的所有外显子和外显子-内含子边界进行了测序。
未发现致病性 CHMP2B 突变。在非编码区域的外显子 1 中发现了一个罕见的多态性（rs36098294）和另外三个先前报道的多态性。
我们的结果证实 CHMP2B 突变不是 FTLD 的常见原因。在芬兰人群中，MAPT 和 PGRN 突变也很少见，这表明其他未知的遗传因素可能在芬兰人群中发挥作用。
