Unbiased targeted next-generation sequencing molecular approach for primary immunodeficiency diseases

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:137

Article

Al-Mousa, Hamoud^1,2,5  Abouelhoda, Mohamed^2,6  Monies, Dorota M.^2,6  Al-Tassan, Nada^2,6  Al-Ghonaium, Abdulaziz¹  Al-Saud, Bandar^1,5  Al-Dhekri, Hasan¹  Arnaout, Rand¹  Al-Muhsen, Saleh^1,7  Ades, Nazema¹  Elshorbagi, Sahar¹  Al Gazlan, Sulaiman³  Sheikh, Farrukh³  Dasouki, Majed²  El-Baik, Lina²  Elamin, Tanzeil²  Jaber, Amal²  Kheir, Omnia²  El-Kalioby, Mohamed²  Subhani, Shazia^2,6  Al Idrissi, Eman⁸  Al-Zahrani, Mofareh⁸  Alhelale, Maryam⁹  Alnader, Noukha²  Al-Otaibi, Afaf²  Kattan, Rana⁶  Al Abdelrahman, Khalid⁶  Al Breacan, Muna M.²  Bin Humaid, Faisal S.²  Wakil, Salma Majid²  Alzayer, Fadi⁴  Al-Dusery, Haya²  Faquih, Tariq²  Al-Hissi, Safa²  Meyer, Brian F.^2,6  Hawwari, Abbas² 

[1] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, POB 3354,MBC 58, Riyadh 11211, Saudi Arabia

[2] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Res Ctr, Riyadh 11211, Saudi Arabia

[3] King Faisal Specialist Hosp & Res Ctr, Dept Med, Riyadh 11211, Saudi Arabia

[4] King Faisal Specialist Hosp & Res Ctr, Dept Pathol & Lab Med, Riyadh 11211, Saudi Arabia

[5] Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia

[6] King Abdulaziz City Sci & Technol, Saudi Human Genome Project, Riyadh, Saudi Arabia

[7] King Saud Univ, Dept Pediat, Riyadh, Saudi Arabia

[8] King Fahad Med City, Dept Pediat, Riyadh, Saudi Arabia

[9] Prince Sultan Mil Med City, Dept Pediat, Riyadh, Saudi Arabia

关键词: Immunodeficiency;    next-generation sequencing;    targeted;    genetic;    primary immunodeficiency;    mutation;    variants;    Saudi;    diagnosis;   

DOI  :  10.1016/j.jaci.2015.12.1310

来源: Elsevier

【 摘 要 】

Background: Molecular genetics techniques are an essential diagnostic tool for primary immunodeficiency diseases (PIDs). The use of next-generation sequencing (NGS) provides a comprehensive way of concurrently screening a large number of PID genes. However, its validity and cost-effectiveness require verification. Objectives: We sought to identify and overcome complications associated with the use of NGS in a comprehensive gene panel incorporating 162 PID genes. We aimed to ascertain the specificity, sensitivity, and clinical sensitivity of the gene panel and its utility as a diagnostic tool for PIDs. Methods: A total of 162 PID genes were screened in 261 patients by using the Ion Torrent Proton NGS sequencing platform. Of the 261 patients, 122 had at least 1 known causal mutation at the onset of the study and were used to assess the specificity and sensitivity of the assay. The remaining samples were from unsolved cases that were biased toward more phenotypically and genotypically complicated cases. Results: The assay was able to detect the mutation in 117 (96%) of 122 positive control subjects with known causal mutations. For the unsolved cases, our assay resulted in a molecular genetic diagnosis for 35 of 139 patients. Interestingly, most of these cases represented atypical clinical presentations of known PIDs. Conclusions: The targeted NGS PID gene panel is a sensitive and cost-effective diagnostic tool that can be used as a first-line molecular assay in patients with PIDs. The assay is an alternative choice to the complex and costly candidate gene approach, particularly for patients with atypical presentation of known PID genes.

【 授权许可】

Free