Objective:To investigate the value of minigene splicing variant analysis in the diagnosis of phosphomannomutase 2-congenital disorder of glycosylation(PMM2-CDG),and to explore the impact of a novel splicing-site variant on the transcript products of the PMM2 gene.Methods:High-throughput sequencing was performed on a PMM2-CDG patient to identify the genetic etiology.Minigene splicing variant analysis was performed to explore the pathogenicity of a novel splicing-site variant in the PMM2 gene.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG),the pathogenicity of the novel variant was determined.Results:On genetic analysis,the patient was a compound heterozygote of the maternal c.691G>A(p.Val231Met)and the paternal c.447+5G>A variants of the PMM2 gene.On minigene splicing variant analysis,the c.447+5G>A variant resulted in the formation of the aberrant transcript r.348_447del,indicating a pathogenic PMM2 variant.The clinical features of the patient were jaundice of the skin and sclera.The serum total bilirubin,unconjugated bilirubin,and total bile acids were significantly increased,albumin was significantly decreased,while alpha-fetoprotein,ferritin and thyrotropin were elevated.Symptomatic and supportive therapy was given,but the effect was not promising.Conclusion:Minigene splicing variant analysis revealed a new molecular marker for the definitive diagnosis and familial genetic counseling of PMM2-CDG,expanded the PMM2 genetic variant spectrum,and provided laboratory evidences for the clinical diagnosis and treatment of this condition.
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