Centre de génomique humaine, faculté de médecine et de pharmacie, université Mohamed V - Rabat, Rabat, Morocco; Département de génétique médicale, Institut national d'hygiène, 27, avenue Ibn Batouta, BP 769, 11400 Rabat, Morocco.
Centre de génomique humaine, faculté de médecine et de pharmacie, université Mohamed V - Rabat, Rabat, Morocco; Département de génétique médicale, Institut national d'hygiène, 27, avenue Ibn Batouta, BP 769, 11400 Rabat, Morocco.
Curr Res Transl Med. 2017 Jan-Mar;65(1):15-19. doi: 10.1016/j.retram.2016.08.002. Epub 2016 Nov 3.
The discovery of somatic mutations within the gene encoding calreticulin (CALR) in 2013 represented a major milestone in the molecular diagnosis of BCR-ABL negative myeloproliferative neoplasms (MPN). In fact, exome sequencing revealed that most patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) lacking JAK2 or MPL mutations, harbor somatic insertion and/or deletion in exon 9 of CALR gene. In this study, we identified the first CALR gene mutational landscape in Moroccan patients with MPN nonmutated for the JAK2 gene.
We performed Sanger sequencing of exon 9 of CALR gene in blood samples obtained from 33 Moroccan patients with ET or PMF non-mutated for JAK2.
Of the 33 patients analyzed, we detected eight distinct variants in 15 patients (45.4%); six indel mutations, five with type 1 recurrent 52bp deletion, four with type 2 recurrent 5bp insertion and one in frame deletion which was found to be a germline variant suggesting a very rare condition in MPN.
This is the first cohort reported in CALR gene mutation analysis in Morocco. Our results were concordant with studies reported up to date and very encouraging in promoting the molecular diagnosis of myeloproliferative neoplasms in Moroccan patients. Moreover, the presence of a germline in frame deletion in a symptomatic patient should undermine the effectiveness of sizing assays without DNA sequencing in the diagnosis of CALR mutations.
2013 年，在编码钙网蛋白（CALR）的基因中发现体细胞突变，这是 BCR-ABL 阴性骨髓增殖性肿瘤（MPN）分子诊断的一个重要里程碑。事实上，外显子组测序显示，大多数缺乏 JAK2 或 MPL 突变的原发性血小板增多症（ET）或原发性骨髓纤维化（PMF）患者存在 CALR 基因 9 号外显子的插入和/或缺失体细胞突变。在这项研究中，我们鉴定了第一个在 JAK2 基因未突变的摩洛哥 MPN 患者的 CALR 基因突变图谱。
我们对 33 例 ET 或 PMF 患者的血液样本进行了 CALR 基因 9 号外显子的 Sanger 测序，这些患者均未发生 JAK2 突变。
在 33 例患者中，我们在 15 例（45.4%）患者中检测到 8 种不同的变异；6 种插入缺失突变，5 种为 52bp 重复缺失，4 种为 5bp 重复插入，1 种为框内缺失，该缺失被发现是一种种系变异，提示在 MPN 中是一种非常罕见的情况。
这是摩洛哥首例报告的 CALR 基因突变分析队列。我们的结果与迄今为止报道的研究一致，非常有助于促进摩洛哥患者骨髓增殖性肿瘤的分子诊断。此外，在有症状的患者中存在种系框内缺失应削弱无 DNA 测序的大小测定在 CALR 突变诊断中的有效性。
