Analysis of a Chinese pedigree affected with rare heart diseases due to variants of TNNI3 and TAZ genes / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with rare type heart disease.@*METHODS@#A pedigree identified at Shenzhen Maternity and Child Health Care Hospital Affiliated to Southern Medical University on July 9, 2021 was selected as the study subject. Clinical data were collected. Trio-whole exome sequencing (WES) was carried out for the proband and his parents. Candidate variants were validated by Sanger sequencing of his family members and bioinformatic analysis.@*RESULTS@#The proband, a 5-month-old male, was found to have Barth syndrome (dilated myocardiopathy and left ventricular non-compaction). Trio-WES revealed that he has harbored a hemizygous c.542G>A (p.G181A) variant of the TAZ gene, which was inherited from his mother. In addition, his mother, aunt and maternal grandmother were also found to harbor a c.557G>A (p.R186Q) variant of the TNNI3 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.542G>A (p.G181A) variant of the TAZ gene was classified as likely pathogenic (PS2_Strong+PM2_Supporting+PP3), whilst the c.557G>A (p.R186Q) variant of the TNNI3 gene was classified as pathogenic (PP1_Strong+PS4_Strong+PP3+PP4+PM2_Supporting).@*CONCLUSION@#The c.542G>A (p.G181A) variant of the TAZ gene probably underlay the Barth syndrome in the proband, and the c.557G>A (p.R186Q) variant of the TNNI3 gene may be responsible for the hypertrophic cardiomyopathy in his mother, aunt and maternal grandmother. Above finding has expanded the mutational spectrum of the TAZ gene and facilitated the diagnosis of this pedigree.