Clinical And ANO5 Genetic Features In A Chinese Family With Limb Girdle Muscular Dystrophy 2L

Objective:To investigate the clinical features and mutations of ANO5 gene in a Chinese family with limb girdle muscular dystrophy 2L(LGMD2L).Methods:The clinical manifestations and laboratory examinations of patients in this family were analyzed.Peripheral blood was collected from the proband and his five family members,then extracted DNA and finally detected the pathogenic gene through the microarray exon-capture and next-generation sequencing technology of hereditary myopathy.Results:(1)The proband(III 3)was a 60-year-old Chinese man,and his parents were intermarriage.On the age of 57 years old,he showed slight weakness and atrophy in proximal muscle of lower limbs and mild-to-moderate hypertrophy of bilateral gastrocnemius.The laboratory results displayed serum creatine kinase fluctuated between 2618-3468 IU/L(normal range is 38-174 IU/L).Electromyography showed myopathic changes.The muscle MRI revealed atrophy and fat in bilateral biceps femoris muscle,seminmenbranosus,semitendinosus etc.Electrron microscopy discovered: HE staining showed a few atrophy and hypertrophy of muscle fiber,internal nuclei and hyperplasia of the interstitial connective tissue.There were scattered necrosis fibers,but no marked inflammatory cell infiltration and abnormalities in other enzyme histochemical staining were discovered.(2)The family members(III 2,III 11,III 13,III 15)also showed bilateral gastrocnemius hypertrophy in varying degrees,but no obvious weakness and atrophy.And the CK was elevated range from 582.72IU/L to 2630.48IU/L.(3)Microarray exon-capture and next-generation sequencing revealed that the proband(III 3)was a homozygous mutation of c.220C>T in ANO5 gene mutation that has been reported.No other pathogenic mutations were found.In his family III 2,III 11,III 13,III 15 were the same homozygous mutation of c.220C>T in ANO5 gene mutation,however the IV4 was discovered heterozygous mutation of c.220C>T in ANO5 gene.Conclusion:In this Chinese LGMD2 L pedigree,the remarkable clinical features were slight and chronic myopathy,hypertrophy of bilateral gastrocnemius and high CK values.Homozygous mutation of c.220C>T was discovered in pathogenic ANO5 gene.