Splicing mutation in TAZ gene leading to exon skipping and Barth syndrome

Area of Science:

• Genetics and Molecular Biology
• Pediatric Cardiology
• Rare Genetic Disorders

Background:

• Barth syndrome is an X-linked disorder caused by tafazzin (TAZ) gene mutations, leading to cardiolipin deficiency and symptoms like cardiomyopathy and neutropenia.
• Understanding TAZ gene function is crucial for diagnosing and potentially treating Barth syndrome.

Observation:

• A 3-year-old boy presented with dilated cardiomyopathy, neutropenia, and growth retardation, indicative of Barth syndrome.
• Genetic analysis revealed a novel TAZ gene variant, c.239-1_239delinsTT, at the intron 2-exon 3 junction.

Findings:

• Functional studies demonstrated that the c.239-1_239delinsTT variant causes aberrant splicing, excising exon 3 and leading to a frameshift in the tafazzin protein.
• This splicing defect results in a non-functional tafazzin protein, consistent with the pathogenic mechanisms of Barth syndrome.

Implications:

• The identified TAZ variant c.239-1_239delinsTT is classified as pathogenic, expanding the known mutation spectrum for Barth syndrome.
• This finding aids in the genetic diagnosis of Barth syndrome and highlights the importance of investigating splicing defects in TAZ gene-related disorders.