Analysis on clinical phenotype and gene mutation of three cases of dysferlinopathy in two families

Abstract

Objective To investigate clinical phenotype and gene mutation of dysferlinopathy. Methods The clinical manifestations, laboratory, imaging, neurophysiological examinations, myopathology and genetic test of 3 patients with dysferlinopathy in 2 Chinese families were studied retrospectively. Results Dysferlinopathy has various clinical manifestations and different clinical subtypes which may appear in the same family. Case 1 was diagnosed as Miyoshi myopathy (MM), while her father (Case 2) was asymptomatic high serum creatine kinase (CK). Muscle MRI showed different degrees of fatty replacement. EMG revealed myogenic damage. Histological morphology showed myodystrophy. Immunohistochemical staining showed negative dysferlin expression in membrane of muscle cells. DYSF gene test showed nonsense mutation in exon 4 c.331C > T (p.Gln111Ter; Case 1 and Case 2) and frameshift mutation in exon 54 c.6141delC (Case 1), and nonsense mutation in exon 23 c.2311C > T (p.Gln771Ter) and frameshift mutation in exon 27 c.2870-2874delAGACC (Case 3). Conclusions Dysferlinopathy has clinical heterogeneity, which is easily misdiagnosed or missed in diagnosis. Detailed history inquiry, negative dysferlin expression in muscle biopsy and DYSF mutation are helpful for clear and classification diagnosis. DOI: 10.3969/j.issn.1672-6731.2018.07.008

Keywords

• Muscular dystrophies
• Phenotype
• Genes
• Mutation
• Pedigree