Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias
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 th...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-09-01
|
Series: | Frontiers in Cell and Developmental Biology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.715042/full |
id |
doaj-2e23fff923bc4777912de8cb2f309d72 |
---|---|
record_format |
Article |
spelling |
doaj-2e23fff923bc4777912de8cb2f309d722021-09-07T05:16:43ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.715042715042Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal DysplasiasShanshan LvJiao ZhaoLei XiXiaoyun LinChun WangHua YueJiemei GuWeiwei HuWenzhen FuZhanying WeiHao ZhangYunqiu HuShanshan LiZhenlin ZhangGenetic 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.715042/fulltargeted exome sequencinggenetic skeletal dysplasiamolecular diagnosisgenetics evaluationclinical utility |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shanshan Lv Jiao Zhao Lei Xi Xiaoyun Lin Chun Wang Hua Yue Jiemei Gu Weiwei Hu Wenzhen Fu Zhanying Wei Hao Zhang Yunqiu Hu Shanshan Li Zhenlin Zhang |
spellingShingle |
Shanshan Lv Jiao Zhao Lei Xi Xiaoyun Lin Chun Wang Hua Yue Jiemei Gu Weiwei Hu Wenzhen Fu Zhanying Wei Hao Zhang Yunqiu Hu Shanshan Li Zhenlin Zhang Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias Frontiers in Cell and Developmental Biology targeted exome sequencing genetic skeletal dysplasia molecular diagnosis genetics evaluation clinical utility |
author_facet |
Shanshan Lv Jiao Zhao Lei Xi Xiaoyun Lin Chun Wang Hua Yue Jiemei Gu Weiwei Hu Wenzhen Fu Zhanying Wei Hao Zhang Yunqiu Hu Shanshan Li Zhenlin Zhang |
author_sort |
Shanshan Lv |
title |
Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias |
title_short |
Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias |
title_full |
Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias |
title_fullStr |
Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias |
title_full_unstemmed |
Genetics Evaluation of Targeted Exome Sequencing in 223 Chinese Probands With Genetic Skeletal Dysplasias |
title_sort |
genetics evaluation of targeted exome sequencing in 223 chinese probands with genetic skeletal dysplasias |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-09-01 |
description |
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. |
topic |
targeted exome sequencing genetic skeletal dysplasia molecular diagnosis genetics evaluation clinical utility |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.715042/full |
work_keys_str_mv |
AT shanshanlv geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT jiaozhao geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT leixi geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT xiaoyunlin geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT chunwang geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT huayue geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT jiemeigu geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT weiweihu geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT wenzhenfu geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT zhanyingwei geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT haozhang geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT yunqiuhu geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT shanshanli geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias AT zhenlinzhang geneticsevaluationoftargetedexomesequencingin223chineseprobandswithgeneticskeletaldysplasias |
_version_ |
1717764770104344576 |