Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias.
Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias.
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223名中国遗传性骨骼发育不良先证者靶向外显子组测序的遗传学评价
DOI：
10.3389/fcell.2021.715042
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Lv S;Zhao J;Xi L;Lin X;Wang C;Yue H;Gu J;Hu W;Fu W;Wei Z;Zhang H;Hu Y;Li S;Zhang Z
遗传性骨骼发育不良（GSDs）是一种具有复杂表型和高度异质性的疾病，其特征是软骨和骨骼生长异常。GSD的表型多变，给临床诊断带来困难。为了探索靶向外显子组测序（targeted exome sequencing， TES）在GSD诊断中的临床应用，我们招募了223个疑似GSD的先证，并对322个已知致病基因进行了TES检测。经过生物信息学分析，所有候选变异按致病性排序。Sanger测序用于验证先证者和父母中的候选变异，并追踪家庭成员中的变异来源。我们确定了来自24个骨骼疾病组的110/223个先证者的分子诊断，并在48个基因中确认了129个致病/可能致病的变异。总诊断率为49%。分子诊断结果修正25%先证者的诊断，其中粘多糖病和脊椎骨外骺端发育不良更容易被误诊。33%先证者的临床管理也有所改善；21个家庭接受了遗传咨询；4个家庭接受产前遗传学诊断，其中1个家庭检出携带致病变异。结果表明，TES对GSD的诊断率较高，有助于临床医生确认患者的分子诊断，制定治疗方向，开展遗传咨询。TES是一种经济的诊断GSD的方法。
Genetic skeletal dysplasias (GSDs) are a type of disease with complex phenotype and high heterogeneity, characterized by cartilage and bone growth abnormalities. The variable phenotypes of GSD make clinical diagnosis difficult. To explore the clinical utility of targeted exome sequencing (TES) in the diagnosis of GSD, 223 probands with suspected GSD were enrolled for TES with a panel of 322 known disease-causing genes. After bioinformatics analysis, all candidate variants were prioritized by pathogenicity. Sanger sequencing was used to verify candidate variants in the probands and parents and to trace the source of variants in family members. We identified the molecular diagnoses for 110/223 probands from 24 skeletal disorder groups and confirmed 129 pathogenic/likely pathogenic variants in 48 genes. The overall diagnostic rate was 49%. The molecular diagnostic results modified the diagnosis in 25% of the probands, among which mucopolysaccharidosis and spondylo-epi-metaphyseal dysplasias were more likely to be misdiagnosed. The clinical management of 33% of the probands also improved; 21 families received genetic counseling; 4 families accepted prenatal genetic diagnosis, 1 of which was detected to carry pathogenic variants. The results showed that TES achieved a high diagnostic rate for GSD, helping clinicians confirm patients’ molecular diagnoses, formulate treatment directions, and carry out genetic counseling. TES could be an economical diagnostic method for patients with GSD.
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影响因子：
4.5
作者：
Sobreira NL;Cirulli ET;Avramopoulos D;Wohler E;Oswald GL;Stevens EL;Ge D;Shianna KV;Smith JP;Maia JM;Gumbs CE;Pevsner J;Thomas G;Valle D;Hoover-Fong JE;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
4.1
作者：
Uttarilli, Anusha;Shah, Hitesh;Girisha, Katta M.
通讯作者：
Girisha, Katta M.
影响因子：
--
作者：
Ritelli M;Chiarelli N;Dordoni C;Quinzani S;Venturini M;Maroldi R;Calzavara-Pinton P;Colombi M
通讯作者：
Colombi M
影响因子：
5
作者：
Gago-Diaz, Marina;Blanco-Verea, Alejandro;Brion, Maria
通讯作者：
Brion, Maria
影响因子：
6.2
作者：
Stuerznickel, Julian;Jaehn-Rickert, Katharina;Oheim, Ralf
通讯作者：
Oheim, Ralf