Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing

Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recr...

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Main Authors: Shuai Han, Hong Xu, Jinxian Zheng, Junhui Sun, Xue Feng, Yue Wang, Wen Ye, Qing Ke, Yanwei Ren, Shulie Yao, Songying Zhang, Jianfen Chen, Robert C. Griggs, Zhengyan Zhao, Ming Qi, Michele A. Gatheridge
Format: Article
Language:English
Published: Hindawi Limited 2020-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2020/8396429
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spelling doaj-a3b2c818076a44f6a868bd2655f586732020-11-25T02:41:58ZengHindawi LimitedBioMed Research International2314-61332314-61412020-01-01202010.1155/2020/83964298396429Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular TestingShuai Han0Hong Xu1Jinxian Zheng2Junhui Sun3Xue Feng4Yue Wang5Wen Ye6Qing Ke7Yanwei Ren8Shulie Yao9Songying Zhang10Jianfen Chen11Robert C. Griggs12Zhengyan Zhao13Ming Qi14Michele A. Gatheridge15Department of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou 310000, ChinaHangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou 310000, ChinaHangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou 310000, ChinaDepartment of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou 310000, ChinaDepartment of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou 310000, ChinaDIAN Diagnostics, Hangzhou 310000, ChinaHangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou 310000, ChinaDepartment of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, ChinaDIAN Diagnostics, Hangzhou 310000, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Department of Laboratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou 310000, ChinaHangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou 310000, ChinaDepartment of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USADepartment of Child Health Care, Children’s Hospital Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou 310000, ChinaDepartment of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USACarrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum DMD genetic testing in subjects with hyperCKemia, defined as CK>200 U/L. The calculated upper reference limit (97.5th percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. DMD genetic testing was conducted on 62 subjects with sustained serum CK>200 U/L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing.http://dx.doi.org/10.1155/2020/8396429
collection DOAJ
language English
format Article
sources DOAJ
author Shuai Han
Hong Xu
Jinxian Zheng
Junhui Sun
Xue Feng
Yue Wang
Wen Ye
Qing Ke
Yanwei Ren
Shulie Yao
Songying Zhang
Jianfen Chen
Robert C. Griggs
Zhengyan Zhao
Ming Qi
Michele A. Gatheridge
spellingShingle Shuai Han
Hong Xu
Jinxian Zheng
Junhui Sun
Xue Feng
Yue Wang
Wen Ye
Qing Ke
Yanwei Ren
Shulie Yao
Songying Zhang
Jianfen Chen
Robert C. Griggs
Zhengyan Zhao
Ming Qi
Michele A. Gatheridge
Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing
BioMed Research International
author_facet Shuai Han
Hong Xu
Jinxian Zheng
Junhui Sun
Xue Feng
Yue Wang
Wen Ye
Qing Ke
Yanwei Ren
Shulie Yao
Songying Zhang
Jianfen Chen
Robert C. Griggs
Zhengyan Zhao
Ming Qi
Michele A. Gatheridge
author_sort Shuai Han
title Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing
title_short Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing
title_full Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing
title_fullStr Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing
title_full_unstemmed Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing
title_sort population-wide duchenne muscular dystrophy carrier detection by ck and molecular testing
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2020-01-01
description Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum DMD genetic testing in subjects with hyperCKemia, defined as CK>200 U/L. The calculated upper reference limit (97.5th percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. DMD genetic testing was conducted on 62 subjects with sustained serum CK>200 U/L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing.
url http://dx.doi.org/10.1155/2020/8396429
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