一个新兴国家先天性免疫缺陷的基因诊断：对216名摩洛哥患者的回顾性研究
Genetic Diagnosis of Inborn Errors of Immunity in an Emerging Country: a Retrospective Study of 216 Moroccan Patients.
作者信息
Moundir Abderrahmane, Ouair Hind, Benhsaien Ibtihal, Jeddane Leila, Rada Nouredine, Amenzoui Naïma, Jouhadi Zineb, Adnane Fatima, Hafidi Naïma El, Kili Amina, Bourhanbour Drissi Asmaa, Babakhouya Abdeladim, Benmiloud Sarra, Hbibi Mohamed, Benajiba Noufissa, Hida Mustapha, Bouskraoui Mohamed, Mahraoui Chafiq, Admou Brahim, Bakkouri Jalila El, Ailal Fatima, Bousfiha Ahmed Aziz
机构信息
Clinical Immunology, Inflammation and Allergy Laboratory (LICIA), Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
Department of Pediatric Infectious Diseases and Clinical Immunology, A. Harouchi Children Hospital, Ibn Rochd University Hospital, Casablanca, Morocco.
出版信息
J Clin Immunol. 2023 Feb;43(2):485-494. doi: 10.1007/s10875-022-01398-z. Epub 2022 Nov 11.
PURPOSE
Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis.
METHODS
We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant.
RESULTS
A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%).
CONCLUSION
The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI.
目的
基因检测为先天性免疫缺陷（IEI）的临床诊断提供了有力支持。然而，高昂的成本和先进的技术使得低收入国家的大部分患者无法进行这些检测。在本研究中，我们旨在评估摩洛哥在基因检测方面的经验，并报告基因诊断中遇到的主要分子特征和困难。
方法
我们对2010年至2022年间在国家登记处登记的所有进行分子诊断的患者进行了多中心回顾性分析。为了评估新发现突变的影响，我们计算了每个变异的综合注释依赖损耗（CADD）评分和突变显著性临界值（MSC）。
结果
在登记的742例IEI患者中，共有216例（29%）患者获得了基因诊断。所有基因检测均在论文项目（40%）或国际合作（60%）的背景下进行。共鉴定出55种基因缺陷，其中7种为新报道的：SNORA31、TBX21、SPPL2A、TYK2、RLTPR、ZNF341和STAT2功能获得性突变。先天性和固有免疫缺陷的基因诊断更为常见，占比78%，而抗体缺陷的频率较低，占比17.5%。补体缺陷组仅做出了一例基因诊断。最常用的分子技术是桑格测序（37%），其次是靶向基因测序（31%）。
结论
论文项目和合作是有益的，因为它们使我们能够为29%的患者提供明确的基因诊断，并有助于鉴定新的基因缺陷和突变。这些结果为摩洛哥IEI基因诊断的进展提供了见解，这将为改善IEI患者的临床管理提供基线。
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