Author:
Zhang Huili,Li Yaqin,Cheng Qiusheng,Chen Xi,Yu Qiuxia,Li Ze
Abstract
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.
Subject
Neurology (clinical),Neurology
Reference25 articles.
1. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy;Liu;Nat Genet,1998
2. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes;Nguyen;Arch Neurol,2007
3. Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies;Nguyen;Hum Mutat,2005
4. UMD-DYSF, a novel locus specific database for the compilation and interactive analysis of mutations in the dysferlin gene;Blandin;Hum Mutat,2012
5. Correction of pseudoexon splicing caused by a novel intronic dysferlin mutation;Dominov;Ann Clin Transl Neurol,2019
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献