Primary Immunodeficiencies in India: Molecular Diagnosis and the Role of Next-Generation Sequencing.
Primary Immunodeficiencies in India: Molecular Diagnosis and the Role of Next-Generation Sequencing.
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DOI：
10.1007/s10875-020-00923-2
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发表时间：
2021-03
影响因子：
9.1
通讯作者：
Edison ES
中科院分区：
文献类型：
--
作者：
Arunachalam AK;Maddali M;Aboobacker FN;Korula A;George B;Mathews V;Edison ES
原发性免疫缺陷病（PID）是一组临床和遗传异质性疾病，显示种族和地理差异。下一代测序（NGS）是诊断PID的综合工具。虽然PID在印度很常见，但由于财政限制，PID遗传谱的数据有限。该研究旨在描述印度PID患者的临床和遗传谱，并强调在资源有限的环境中采用具有成本效益的PID靶向基因组测序方法的重要性。该研究包括229例临床和实验室特征提示PID的患者。通过桑格测序和NGS靶向定制的基因组进行突变分析。在97名患者中鉴定了涉及42种不同基因的致病性变体，其中BTK和IL12RB1是最常见的突变基因。常染色体隐性遗传和X连锁隐性遗传分别占51.6%和23.7%。与西方世界和中东地区相比，我们的人群中对分枝杆菌疾病（MSMD）和IL12RB1突变的孟德尔易感性更常见。还确定了两名患者与亚型RAG1突变和一名女性与偏斜CYBB突变。另外40例患者的变异被归类为意义不确定的变异（VUS）。该研究表明，在诊断资源有限的国家，有针对性的NGS是一种有效的PID诊断策略。PID的分子诊断有助于遗传咨询和做出治疗决定，包括需要干细胞移植。
Primary immunodeficiency diseases (PIDs) are a group of clinically and genetically heterogeneous disorders showing ethnic and geographic diversities. Next-generation sequencing (NGS) is a comprehensive tool to diagnose PID. Although PID is common in India, data on the genetic spectrum of PIDs are limited due to financial restrictions. The study aims to characterize the clinical and genetic spectrum of PID patients in India and highlight the importance of a cost-effective targeted gene panel sequencing approach for PID in a resource-limited setting. The study includes 229 patients with clinical and laboratory features suggestive of PIDs. Mutation analysis was done by Sanger sequencing and NGS targeting a customized panel of genes. Pathogenic variants were identified in 97 patients involving 42 different genes with BTK and IL12RB1 being the most common mutated genes. Autosomal recessive and X-linked recessive inheritance were seen in 51.6% and 23.7% of patients. Mendelian susceptibility to mycobacterial diseases (MSMD) and IL12RB1 mutations was more common in our population compared to the Western world and the Middle East. Two patients with hypomorphic RAG1 mutations and one female with skewed CYBB mutation were also identified. Another 40 patients had variants classified as variants of uncertain significance (VUS). The study shows that targeted NGS is an effective diagnostic strategy for PIDs in countries with limited diagnostic resources. Molecular diagnosis of PID helps in genetic counseling and to make therapeutic decisions including the need for a stem cell transplantation.
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影响因子：
9.1
作者：
Bousfiha A;Jeddane L;Picard C;Ailal F;Bobby Gaspar H;Al-Herz W;Chatila T;Crow YJ;Cunningham-Rundles C;Etzioni A;Franco JL;Holland SM;Klein C;Morio T;Ochs HD;Oksenhendler E;Puck J;Tang MLK;Tangye SG;Torgerson TR;Casanova JL;Sullivan KE
通讯作者：
Sullivan KE
影响因子：
9.1
作者：
Al-Tamemi, Salem;Naseem, Shafiq Ur Rehman;Dennison, David
通讯作者：
Dennison, David
影响因子：
9.8
作者：
Conley, ME;Mathias, D;Rohrer, J
通讯作者：
Rohrer, J
影响因子：
3.4
作者：
Arun, A. Kumar;Senthamizhselvi, Anandan;Balasubramanian, Poonkuzhali
通讯作者：
Balasubramanian, Poonkuzhali
影响因子：
5.8
作者：
Döffinger, R;Altare, F;Casanova, JL
通讯作者：
Casanova, JL