Genetic analysis of a Chinese pedigree affected with Mucopolysaccharidosis type ⅢA / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A).@*METHODS@#A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site.@*RESULTS@#The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range.@*CONCLUSION@#The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.

Correlation analysis of single nucleotide polymorphisms in autophage-related 5 ( ATG[STHZ]5[STBZ] ) gene promoter with acute myocardial infarction / 临床检验杂志

Objective@#To investigate the correlation of single nucleotide polymorphisms (SNPs) in autophage-related 5 ( ATG5 ) gene promoter with acute myocardial infarction (AMI). @*Methods@#The SNPs of ATG5 gene promoter were detected by polymerase chain reaction (PCR) and Sanger sequencing. The typing and correlation of SNPs in 378 AMI patients and 374 healthy controls were analyzed by Chi-square test, Logistic regression analysis and haplotype analysis. @*Results@#Two SNPs of ATG5 gene promoter, rs506027 (OR=1.4, 95% CI \[0.6-3.0\], P=0.411) and rs510432 (OR=1.6, 95% CI \[0.7-3.4\], P=0.275), were found. They didn′t increase the susceptibility of AMI, and the haplotype associated with AMI was not found in the two SNPs. @*Conclusion@#The polymorphism of ATG5 gene promoter isn′t associated with the susceptibility of AMI.