Barth syndrome (BTHS) is a rare genetic disorder characterized by various types of cardiomyopathy, neutropenia, failure to thrive, skeletal myopathy, and 3-methylglutaconic aciduria. BTHS is caused by loss-of-function mutations in the tafazzin (TAZ) gene located on chromosome Xq28, leading to cardiolipin deficiency. We report a 13-month-old boy with BTHS who had a novel de novo mutation in the TAZ gene. To the best of our knowledge, this is the first reported case of a BTHS patient with a de novo mutation in Korea. This report will contribute towards expanding the knowledge on the mutation spectrum of the TAZ gene in BTHS.
Barth Syndrome* ; Cardiolipins ; Cardiomyopathies ; Failure to Thrive ; Humans ; Infant ; Korea ; Male ; Muscular Diseases ; Neutropenia

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.
Female ; Humans ; Infant ; Male ; Pregnancy ; Barth Syndrome ; Cardiomyopathy, Hypertrophic ; East Asian People ; Heart Diseases ; Pedigree

OBJECTIVE: To carry out genetic testing for a family with two pregnancies affected with hydrops fetalis and dilated cardiomyopathy (DCM) of the fetus. METHODS: DNA was extracted from fetal tissue as well as peripheral blood samples from the couple. Single nucleotide polymorphism array (SNP array) and next-generation sequencing (NGS) were carried out to screen potential mutation. Suspected mutation was validated with PCR and Sanger sequencing. RESULTS: The manifestation of fetal echocardiography was consistent with DCM. No obvious abnormality was found by SNP array analysis. A hemizygous c.481G>A (p.G161R) mutation of the TAZ gene was detected in the male fetus by NGS and confirmed by Sanger sequencing. The mutation was inherited from his mother. CONCLUSION Barth syndrome due to the c.481G>A mutation of the TAZ gene probably underlies the recurrent hydrops fetalis and fetal DCM in this family.
Barth Syndrome ; genetics ; Cardiomyopathy, Dilated ; genetics ; Echocardiography ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Hydrops Fetalis ; genetics ; Male ; Mutation ; Pregnancy ; Transcription Factors ; genetics

Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by a hypertrabeculation of the left ventricle. Patients may present with heart failure, arrhythmia, and thromboembolism. LVNC may be isolated or associated with congenital heart defects. The first discovered genetic cause of isolated LVNC was Barth syndrome (BTHS), an X-linked disorder caused by taffazin (TAZ) gene mutation. BTHS is characterized by cardiomyopathy, neutropenia, skeletal myopathy, and growth delay. A newborn male baby was referred to Soonchunhyang University Cheonan Hospital due to cyanosis and dyspnea. Based on findings of cardiomegaly, ST depression, and elevated cardiac enzyme, echocardiography was done, which revealed a hypocontractile, enlarged left ventricle with distinctive trabeculation in the apex. Heparinization for the treatment of myocardial infarction and continuous infusion of milrinone was started. During hospitalization, the TAZ gene mutation was detected in the patient, his mother, and elder sister. After 3 months, the patient was discharged with heart failure medication and aspirin.
Arrhythmias, Cardiac ; Aspirin ; Barth Syndrome* ; Cardiomegaly ; Cardiomyopathies ; Chungcheongnam-do ; Cyanosis ; Depression ; Dyspnea ; Echocardiography ; Heart Defects, Congenital ; Heart Failure ; Heart Ventricles ; Heparin ; Hospitalization ; Humans ; Infant, Newborn* ; Isolated Noncompaction of the Ventricular Myocardium ; Male ; Milrinone ; Mothers ; Muscular Diseases ; Myocardial Infarction* ; Neutropenia ; Siblings ; Thromboembolism

A 14-month-old boy was transferred because of dilated and hypertrophied left ventricle, neutropenia, and developmental delay. After checking computed tomographic angiography with contrast-dye, the patient showed acute exacerbation and finally died from multi-organ failure despite intensive cares. From genetic analysis, we revealed that the patient had Barth syndrome and found a novel hemizygous frame shift mutation in his TAZ gene, c.227delC (p.Pro76LeufsX7), which was inherited from his mother. Herein, we report a patient with Barth syndrome who had a novel mutation in TAZ gene and experienced unexpected acute exacerbation after contrast dye injection for computed tomographic angiography.
Acidosis/etiology ; Acute Disease ; Adolescent ; Barth Syndrome/diagnosis/*genetics ; Contrast Media/adverse effects/*diagnostic use ; Frameshift Mutation ; Heart Failure/etiology ; Homozygote ; Humans ; Male ; Mutation ; Pedigree ; Sequence Analysis, DNA ; Tomography, X-Ray Computed ; Transcription Factors/*genetics