Coexistence of Multiple Gene Variants in Some Patients with Erythrocytoses.

IF 2 4区医学 Q3 HEMATOLOGY Mediterranean Journal of Hematology and Infectious Diseases Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI:10.4084/MJHID.2024.021

Andrea Benetti, Irene Bertozzi, Giulio Ceolotto, Irene Cortella, Daniela Regazzo, Giacomo Biagetti, Elisabetta Cosi, Maria Luigia Randi

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Abstract

Background: Erythrocytosis is a relatively common condition; however, a large proportion of these patients (70%) remain without a clear etiologic explanation.

Methods: We set up a targeted NGS panel for patients with erythrocytosis, and 118 sporadic patients with idiopathic erythrocytosis were studied.

Results: In 40 (34%) patients, no variant was found, while in 78 (66%), we identified at least one germinal variant; 55 patients (70.5%) had 1 altered gene, 18 (23%) had 2 alterations, and 5 (6.4%) had 3. An altered HFE gene was observed in 51 cases (57.1%), EGLN1 in 18 (22.6%) and EPAS1, EPOR, JAK2, and TFR2 variants in 7.7%, 10.3%, 11.5%, and 14.1% patients, respectively. In 23 patients (19.45%), more than 1 putative variant was found in multiple genes.

Conclusions: Genetic variants in patients with erythrocytosis were detected in about 2/3 of our cohort. An NGS panel including more candidate genes should reduce the number of cases diagnosed as "idiopathic" erythrocytosis in which a cause cannot yet be identified. It is known that HFE variants are common in idiopathic erythrocytosis. TFR2 alterations support the existence of a relationship between genes involved in iron metabolism and impaired erythropoiesis. Some novel multiple variants were identified. Erythrocytosis appears to be often multigenic.

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一些红细胞增多症患者同时存在多种基因变异。

背景：红细胞增多症是一种相对常见的疾病；然而，其中很大一部分患者（70%）仍然没有明确的病因：我们为红细胞增多症患者建立了一个有针对性的 NGS 图谱，并对 118 例特发性红细胞增多症散发性患者进行了研究：结果：在 40 例（34%）患者中未发现任何变异，而在 78 例（66%）患者中，我们发现了至少一个基因变异；55 例（70.5%）患者有 1 个基因改变，18 例（23%）有 2 个基因改变，5 例（6.4%）有 3 个基因改变。51例（57.1%）患者的HFE基因发生了改变，18例（22.6%）患者的EGLN1基因发生了改变，7.7%、10.3%、11.5%和14.1%的患者分别出现了EPAS1、EPOR、JAK2和TFR2变异。23名患者（19.45%）在多个基因中发现了一个以上的推测变异：结论：在我们的队列中，约有 2/3 的红细胞增多症患者检测到了基因变异。包含更多候选基因的 NGS 面板应能减少被诊断为 "特发性 "红细胞增多症但尚未找到病因的病例数量。众所周知，HFE 变异在特发性红细胞增多症中很常见。TFR2变异支持铁代谢相关基因与红细胞生成障碍之间存在关系。还发现了一些新的多重变异。红细胞增多症似乎往往是多基因性的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mediterranean Journal of Hematology and Infectious Diseases Medicine-Hematology

CiteScore

4.20

自引率

6.20%

发文量

113

审稿时长

12 weeks

期刊介绍： Reciprocal interdependence between infectious and hematologic diseases (malignant and non-malignant) is well known. This relationship is particularly evident in Mediterranean countries. Parasitosis as Malaria, Leishmaniosis, B Hookworms, Teniasis, very common in the southeast Mediterranean area, infect about a billion people and manifest prevalently with anemia so that they are usually diagnosed mostly by experienced hematologist on blood or bone marrow smear. On the other hand, infections are also a significant problem in patients affected by hematological malignancies. The blood is the primary vector of HIV infection, which otherwise manifest with symptoms related to a reduction in T lymphocytes. In turn, infections can favor the insurgency of hematological malignancies. The causative relationship between Epstein-Barr virus infection, Helicobacter pylori, hepatitis C virus, HIV and lymphoproliferative diseases is well known.