Screening And Diagnosis Of Fabry Disease And Analysis Of Clinical And Genetic Characteristics In Pedigrees

Part ?:Screening and diagnosis of Fabry diseaseObjective:The purpose of this study was to learn about the prevalence of Fabry disease in male patients with hypertrophic cardiomyopathy in Suzhou and to identify the mutation type of GLA gene.Methods:We collected clinical data and measured the concentration of a-galactosidase in 74 male patients in the Suzhou area of China who were diagnosed with hypertrophic cardiomyopathy for their unexplained left ventricular thickness?15mm in the First Affiliated Hospital of Soochow University from April to December 2018.If the patients' clinical symptoms are associated with Fabry disease,accompanied by low enzyme concentration,GLA gene testing was performed to confirm whether they had genetic mutations.The biological information software was used to confirm the diagnosis by analysing the pathogenicity of gene mutations.Results:Two male patients had clinical manifestations of Fabry disease and their enzyme concentration decreased.They were highly suspected of Fabry disease.Both patients had atypical symptoms such as hypohidrosis,limb pain,hearing loss,rash and corneal opacity.They had renal failure or cardiac hypertrophy as adults.At the same time,a novel missense mutation c.827G>T(p.S276I)and a novel nonsense mutation c.298A>T(p.R100X)were identified.The results of using three bioinformatics software include Polyphen2?SI-FT and Mutation Taster showed they had pathogenic mutations.And combing with typical clinical symptoms,Fabry disease can be clearly diagnosed.Conclusions:In Suzhou area two patients with Fabry disease were detected in 74 male who were diagnosed with hypertrophic cardiomyopathy.We should consider Fabry disease for male patients with unexplained left ventricular wall thickening.Two novel genetic mutation suspected of causing this disease were revealed.Part ?:A clinical and genetic study on Familial Fabry diseaseObjective:To investigate the two families diagnosed with Fabry disease,and explore the correlation between genotype and phenotype.Methods:The clinical data of the 16 family members of 2 proband were collected,including general information,electrocardiogram,echocardiography and so on.GLA gene was amplified by polymerase chain reaction from peripheral blood of 14 members and confirmed by purified sequencing site.Combing clinical date and genetic test results,the members of Fabry disease were identified.Complete family genetic trees were drawn,and possible genetic pattern was identified.We analyzed their clinical phenotypes and mutation genotypes to definite the pathogenicity of the mutations according to the ACGM guideline.Results:Genetic testing showed that five female members of the two families carried mutations at the same site.The family pedigree was drawn from clinical data of the family members.They showed that the disease is consistent with X chromosome inheritance and the clinical manifestations of patients in the family are significantly different.At the early stage,the clinical symptoms of male patients were more typical than women.Both male and female patients might have the heart and kidney damage at the late stage.But the age of onset of men were earlier.According to ACGM analysis p.S276I was a likely pathogenic mutation,and p.R100X was a pathogenic mutation.Conclusions:Two new families with Fabry disease were found in Suzhou,China.Two different types of gene mutations could show similar clinical symptoms,and the same type of gene mutation might have different clinical manifestations in the same family.