A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA)

被引：74

作者：

Liang, Qiaowei ^{[1
]}

Gu, Wanqian ^{[2
]}

Chen, Ping ^{[3
]}

Li, Yuezhen ^{[4
]}

Liu, Yanqiu ^{[5
]}

Tian, Mao ^{[6
]}

Zhou, Qiaomiao ^{[7
]}

Qi, Hongbo ^{[8
]}

Zhang, Yuhong ^{[9
]}

He, Jun ^{[10
]}

Li, Qing ^{[11
]}

Tang, Lingfang ^{[12
]}

Tang, Juan ^{[13
]}

Teng, Yanling ^{[1
]}

Zhou, Yulin ^{[14
]}

Huang, Shengwen ^{[15
]}

Lu, Zongjie ^{[16
]}

Xu, Mengnan ^{[4
]}

Hou, Wei

Huang, Ting ^{[5
]}

Li, Youqiong ^{[6
]}

Li, Rong ^{[8
]}

Hu, Lanping ^{[10
]}

Li, Shaoying ^{[11
]}

Guo, Qiwei ^{[14
]}

Zhuo, Zhaozhen ^{[15
]}

Mou, Yan ^{[16
]}

Cram, David S. ^{[4
]}

Wu, Lingqian ^{[1
,17
]}

机构：

[1] Hunan Jiahui Genet Hosp, Dept Mol Genet, Changsha, Peoples R China

[2] Yunnan Maternal & Child Hlth Care Hosp, Dept Reprod Genet, Kunming, Yunnan, Peoples R China

[3] Guangxi Med Univ, Chinese Acad Med Sci, Guangxi Key Lab Thalassemia Res, Affiliated Hosp 1,Key Lab Thalassemia Med, Nanning, Peoples R China

[4] Berry Genom Corp, Beijing, Peoples R China

[5] Jiangxi Maternal & Child Hlth Hosp, Prenatal Diag Ctr, Nanchang, Jiangxi, Peoples R China

[6] Peoples Hosp Guangxi Zhuang Autonomous Reg, Ctr Med Genet & Prenatal Diag, Nanning, Peoples R China

[7] Hainan Women & Childrens Med Ctr, Dept Genet & Prenatal Diag, Haikou, Hainan, Peoples R China

[8] Chongqing Med Univ, Dept Obstet & Gynecol, Chongqing, Peoples R China

[9] Chongqing Med Univ, Ctr Clin Mol Med Detect, Affiliated Hosp 1, Chongqing, Peoples R China

[10] Changsha Hosp Maternal & Child Hlth Care Genet Eu, Dept Mol Genet, Changsha, Peoples R China

[11] Guangzhou Med Univ, Key Lab Major Obstetr Dis Guangdong Prov, Affiliated Hosp 3, Guangzhou, Peoples R China

[12] Guilin Women & Children Hlth Care Hosp, Dept Pregnancy Hlth, Guilin, Peoples R China

[13] Guilin Women & Children Hlth Care Hosp, Lab Genet & Metabolism, Guilin, Peoples R China

[14] Xiamen Univ, Women & Childrens Hosp, United Diagnost & Res Ctr Clin Genet, Sch Med & Sch Publ Hlth, Xiamen, Peoples R China

[15] Guizhou Prov Peoples Hosp, Dept Genet & Prenatal Diag, Guiyang, Peoples R China

[16] Suining Cent Hosp, Dept Obstet, Suining, Peoples R China

[17] Cent South Univ, Ctr Med Genet, Hunan Key Lab Med Genet, Sch Life Sci, Changsha, Peoples R China

来源：

JOURNAL OF MOLECULAR DIAGNOSTICS | 2021年 / 23卷 / 09期

关键词：

BETA-THALASSEMIA; ALPHA; DIAGNOSIS; HEMOGLOBINOPATHIES; VARIANTS; GENETICS;

D O I：

10.1016/j.jmoldx.2021.06.008

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

The aim of the study was to assess the clinical utility of a third-generation sequencing (TGS) approach termed comprehensive analysis of thalassemia alleles (CATSA) for identifying both alpha and beta thalassemia genetic carrier status. Prospective blood samples (n = 1759) with abnormal hemoglobin parameters were screened for pathogenic thalassemia variants by CATSA on the PacBio TGS platform. In 1159 individuals, a total of 1317 pathogenic thalassemia variants were identified and confirmed by independent PCR-based tests. Of the total thalassemia variants detected, the alpha-variant_(SEA) (35.4%) and beta-variant c.126_129delCITT (15%) were the most common. CATSA was also able to detect three types of rare HBA structural variants as well as five rare HBA2, three HBA1, and 10 HBB single-nucleotide variations/insertions and deletions. Compared with standard thalassemia variant PCR panel testing, CATSA identified all panel variants present, with no falsenegative results. Carrier assignment was improved through identification of rare variants missed by the panel test. On the basis of allelic coverage, reliability, and accuracy, TGS with long-range PCR presents a comprehensive approach with the potential to provide a universal solution for thalassemia genetic carrier screening. It is proposed that CATSA has immediate clinical utility as an effective carrier screening approach for at-risk couples.

引用

页码：1195 / 1204

页数：10

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