%0 Case Reports
%T A case of infantile Barth syndrome with severe heart failure: Importance of splicing variants in the TAZ gene.
%A Takeda A
%A Ueki M
%A Abe J
%A Maeta K
%A Horiguchi T
%A Yamazawa H
%A Izumi G
%A Chida-Nagai A
%A Sasaki D
%A Tsujioka T
%A Sato I
%A Shiraishi M
%A Matsuo M
%J Mol Genet Genomic Med
%V 11
%N 7
%D 2023 07 25
%M 37186429
%F 2.473
%R 10.1002/mgg3.2190
%X Barth syndrome (BTHS) is an X-linked disorder characterized by cardiomyopathy, skeletal myopathy, and 3-methylglutaconic aciduria. The causative pathogenic variants for BTHS are in TAZ, which encodes a putative acyltransferase named tafazzin and is involved in the remodeling of cardiolipin in the inner mitochondrial membranes. Pathogenic variants in TAZ result in mitochondrial structural and functional abnormalities. We report a case of infantile BTHS with severe heart failure, left ventricular noncompaction, and lactic acidosis, having a missense c.640C>T (p.His214Tyr) variant in TAZ, which is considered a pathogenic variant based on the previously reported amino acid substitution at the same site (c.641A>G, p.His214Arg). However, in this previously reported case, heart function was compensated and not entirely similar to the present case. Silico prediction analysis suggested that c.640C>T could alter the TAZ messenger RNA (mRNA) splicing process. TAZ mRNAs in isolated peripheral mononuclear cells from the patient and in vitro splicing analysis using minigenes of TAZ found an 8 bp deletion at the 3' end of exon 8, which resulted in the formation of a termination codon in the coding region of exon 9 (H214Nfs*3). These findings suggest that splicing abnormalities should always be considered in BTHS.