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

被引：96

作者：

Al-Mousa, Hamoud ^{[1
,2
,5
]}

Abouelhoda, Mohamed ^{[2
,6
]}

Monies, Dorota M. ^{[2
,6
]}

Al-Tassan, Nada ^{[2
,6
]}

Al-Ghonaium, Abdulaziz ^{[1
]}

Al-Saud, Bandar ^{[1
,5
]}

Al-Dhekri, Hasan ^{[1
]}

Arnaout, Rand ^{[1
]}

Al-Muhsen, Saleh ^{[1
,7
]}

Ades, Nazema ^{[1
]}

Elshorbagi, Sahar ^{[1
]}

Al Gazlan, Sulaiman ^{[3
]}

Sheikh, Farrukh ^{[3
]}

Dasouki, Majed ^{[2
]}

El-Baik, Lina ^{[2
]}

Elamin, Tanzeil ^{[2
]}

Jaber, Amal ^{[2
]}

Kheir, Omnia ^{[2
]}

El-Kalioby, Mohamed ^{[2
]}

Subhani, Shazia ^{[2
,6
]}

Al Idrissi, Eman ^{[8
]}

Al-Zahrani, Mofareh ^{[8
]}

Alhelale, Maryam ^{[9
]}

Alnader, Noukha ^{[2
]}

Al-Otaibi, Afaf ^{[2
]}

Kattan, Rana ^{[6
]}

Al Abdelrahman, Khalid ^{[6
]}

Al Breacan, Muna M. ^{[2
]}

Bin Humaid, Faisal S. ^{[2
]}

Wakil, Salma Majid ^{[2
]}

Alzayer, Fadi ^{[4
]}

Al-Dusery, Haya ^{[2
]}

Faquih, Tariq ^{[2
]}

Al-Hissi, Safa ^{[2
]}

Meyer, Brian F. ^{[2
,6
]}

Hawwari, Abbas ^{[2
]}

机构：

[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

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2016年 / 137卷 / 06期

关键词：

Immunodeficiency; next-generation sequencing; targeted; genetic; primary immunodeficiency; mutation; variants; Saudi; diagnosis; WHOLE-EXOME; IDENTIFICATION; MUTATIONS; DIAGNOSIS; DEFECTS; CAPTURE;

D O I：

10.1016/j.jaci.2015.12.1310

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

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.

引用

页码：1780 / 1787

页数：8

共 24 条

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