Clinical and genetic characteristics of female dystrophinopathy carriers

Zhong,Jingzi; Xie,Yanshu; Bhandari,Vidata; Chen,Gang; Dang,Yiwu; Liao,Haixia; Zhang,Jiapeng; Lan,Dan

doi:10.3892/mmr.2019.9982

Clinical and genetic characteristics of female dystrophinopathy carriers

Authors:
- Jingzi Zhong
- Yanshu Xie
- Vidata Bhandari
- Gang Chen
- Yiwu Dang
- Haixia Liao
- Jiapeng Zhang
- Dan Lan
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Affiliations: Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: February 25, 2019 https://doi.org/10.3892/mmr.2019.9982
Pages: 3035-3044
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to determine the genetic status of manifesting carriers (MCs) of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) and asymptomatic carriers with a family history of DMD/BMD, and identify potential simple and reliable methods for screening dystrophinopathy carriers. Clinical data from probable carriers and MCs were collected and analyzed. MCs underwent multiplex ligation‑dependent probe amplification (MLPA) for dystrophin gene exons combined with muscle disease panel test based on a next‑generation sequencing (NGS) platform. In addition, the status of probable carriers was determined by MLPA or Sanger sequencing, according to the mutations of probands. A total of 154 female were enrolled, among which 78 cases were found to be carriers, including 4 MCs and 74 asymptomatic female carriers. The 4 MCs exhibited duplication mutations. Among the 74 asymptomatic carriers, 41.89% harbored deletion mutations, including 2 cases with suspected germline mosaicism and no mutation in the dystrophin gene, while 44.59% harbored point mutations in exons and only 10 cases (13.51%) carried duplication mutations. The area under the receiver operating characteristic (ROC) curve of creatine kinase (CK) was 0.822, with a sensitivity of 65.38% and specificity of 92.1%. In addition, DMD was positively correlated with the CK, alanine transaminase and aspartate transaminase levels of the carriers. MLPA for exons of the dystrophin gene, along with NGS and Sanger sequencing, was effective for the diagnosis of MCs and for determining the status of probable carriers. The ROC curve analysis also demonstrated that CK level was an excellent predictor for distinguishing DMD/BMD carriers.

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