PDF(Pubmed)
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.
摘要：
Barth综合征（BTHS）是一种以心肌病为特征的X连锁疾病，骨骼肌病,和3-甲基谷氨酸尿症。BTHS的致病变异在TAZ，它编码一种名为tafazzin的推定酰基转移酶，并参与线粒体内膜心磷脂的重塑。TAZ中的致病变体导致线粒体结构和功能异常。我们报告一例婴儿BTHS伴严重心力衰竭，左心室不紧密,和乳酸性酸中毒,有一个误解c.640C>T(p.His214Tyr）在TAZ中的变体，这被认为是基于先前报道的在相同位点的氨基酸取代的致病变体（c.641A>G，p.His214Arg)。然而,在以前报道的这个案例中,心功能得到补偿，与本案并不完全相似。Silico预测分析表明c.640C>T可以改变TAZ信使RNA（mRNA）的剪接过程。来自患者的分离的外周单核细胞中的TAZmRNA和使用TAZ的小基因进行的体外剪接分析发现在外显子8的3'末端有8bp的缺失，这导致在外显子9的编码区形成终止密码子(H214Nfs*3)。这些发现表明，在BTHS中应始终考虑剪接异常。
