Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses
Objective: Dysferlin deficiency causes dysferlinopathy. This study aimed to expand the mutational spectrum of dysferlinopathies, to further study one case with diagnostic ambiguity, and to identify the diagnostic value of dysferlin expression in total peripheral blood mononuclear cells (PBMC).Method...
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doaj-107d7a604b63483b97497cea7a08ac192021-02-04T07:34:38ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-02-011110.3389/fneur.2020.540098540098Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic AnalysesHuili Zhang0Yaqin Li1Qiusheng Cheng2Xi Chen3Qiuxia Yu4Ze Li5Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Neurology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaPrenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaObjective: Dysferlin deficiency causes dysferlinopathy. This study aimed to expand the mutational spectrum of dysferlinopathies, to further study one case with diagnostic ambiguity, and to identify the diagnostic value of dysferlin expression in total peripheral blood mononuclear cells (PBMC).Methods: The clinical and molecular profiles of dysferlinopathies in eight Chinese patients were evaluated. We also conducted magnetic resonance imaging (6/8) and determined dysferlin protein expression in muscle (7/8) and PBMC (3/8).Results: Nine of the 13 DYSF mutations identified were novel. One patient was homozygous for the Gln111Ter mutation by genomic DNA sequencing but was found to be heterozygous by sequencing of cDNA from total PBMC. A daughter of this patient did not carry any Gln111Ter mutation. Abnormal muscle MRI with predominant involvement of the medial gastrocnemius and soleus muscle was observed in 5/6 patients. Dysferlin levels were significantly reduced (immunohistochemistry/immunoblot) or absent (immunohistochemistry) in muscle and total PBMC (26–39%) for most patients. Sarcoplasmic accumulation of dysferlin was detected in one patient.Conclusion: Genomic DNA sequencing detects frequent homozygous mutations, while fewer heterozygous mutations in cDNA are detected after posttranscription. Total PBMC may serve as an alternative to confirm diagnosis and to guide further testing in dysferlinopathies. Our results contribute to the mutational spectrum of dysferlinopathies.https://www.frontiersin.org/articles/10.3389/fneur.2020.540098/fulldysferlinopathyDYSFMRIdysferlinperipheral blood mononuclear cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huili Zhang Yaqin Li Qiusheng Cheng Xi Chen Qiuxia Yu Ze Li |
spellingShingle |
Huili Zhang Yaqin Li Qiusheng Cheng Xi Chen Qiuxia Yu Ze Li Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses Frontiers in Neurology dysferlinopathy DYSF MRI dysferlin peripheral blood mononuclear cells |
author_facet |
Huili Zhang Yaqin Li Qiusheng Cheng Xi Chen Qiuxia Yu Ze Li |
author_sort |
Huili Zhang |
title |
Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses |
title_short |
Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses |
title_full |
Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses |
title_fullStr |
Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses |
title_full_unstemmed |
Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses |
title_sort |
abnormal expression of dysferlin in blood monocytes supports primary dysferlinopathy in patients confirmed by genetic analyses |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2021-02-01 |
description |
Objective: Dysferlin deficiency causes dysferlinopathy. This study aimed to expand the mutational spectrum of dysferlinopathies, to further study one case with diagnostic ambiguity, and to identify the diagnostic value of dysferlin expression in total peripheral blood mononuclear cells (PBMC).Methods: The clinical and molecular profiles of dysferlinopathies in eight Chinese patients were evaluated. We also conducted magnetic resonance imaging (6/8) and determined dysferlin protein expression in muscle (7/8) and PBMC (3/8).Results: Nine of the 13 DYSF mutations identified were novel. One patient was homozygous for the Gln111Ter mutation by genomic DNA sequencing but was found to be heterozygous by sequencing of cDNA from total PBMC. A daughter of this patient did not carry any Gln111Ter mutation. Abnormal muscle MRI with predominant involvement of the medial gastrocnemius and soleus muscle was observed in 5/6 patients. Dysferlin levels were significantly reduced (immunohistochemistry/immunoblot) or absent (immunohistochemistry) in muscle and total PBMC (26–39%) for most patients. Sarcoplasmic accumulation of dysferlin was detected in one patient.Conclusion: Genomic DNA sequencing detects frequent homozygous mutations, while fewer heterozygous mutations in cDNA are detected after posttranscription. Total PBMC may serve as an alternative to confirm diagnosis and to guide further testing in dysferlinopathies. Our results contribute to the mutational spectrum of dysferlinopathies. |
topic |
dysferlinopathy DYSF MRI dysferlin peripheral blood mononuclear cells |
url |
https://www.frontiersin.org/articles/10.3389/fneur.2020.540098/full |
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