In:
Molecular Genetics & Genomic Medicine, Wiley, Vol. 11, No. 7 ( 2023-07)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2324-9269
,
2324-9269
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2734884-2
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