Department of Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Pediatr Res. 2012 Oct;72(4):432-7. doi: 10.1038/pr.2012.92. Epub 2012 Jul 13.
We report a new mutation in the human DNAJC19 gene that causes early onset dilated cardiomyopathy syndrome (DCMA).
Two brothers of Finnish origin presented with an unusual combination of early onset dilated cardiomyopathy syndrome, a disease which was associated with cardiac noncompaction, microcytic anemia, ataxia, male genital anomalies and methylglutaconic aciduria type V. Suspicion of a DCMA syndrome prompted sequencing of the human DNAJC19 gene.
Sequencing of the human DNAJC19 gene showed a homozygous single nucleotide (A) deletion in alanine 63 coding triplet in exon 6, which does not immediately cause amino acid change but leads 11 amino acids later to a stop codon and to premature termination of the peptide. This DNAJC19 protein is located in the inner mitochondrial membrane and has been shown to function as a mitochondrial chaperone.
This is the first clinical report of DCMA syndrome, a human DNAJC19 deficiency, that is related to cases of severe dilated cardiomyopathy diagnosed in Europe. DNAJC19 deficiency causes a relatively specific finding in urinary organic acid analysis (methylglutaconic aciduria type V), which together with the clinical features of the ensuing cardiac disease, allows for effective screening before undertaking molecular genetic analysis.
我们报道了一种新的人类 DNAJC19 基因突变，该突变导致早发性扩张型心肌病综合征（DCMA）。
两名芬兰血统的兄弟表现出一种不寻常的早发性扩张型心肌病综合征组合，这种疾病与心脏非致密化、小细胞性贫血、共济失调、男性生殖器异常和甲基戊二酸尿症 V 型有关。怀疑为 DCMA 综合征后，我们对人类 DNAJC19 基因进行了测序。
人类 DNAJC19 基因的测序显示，第 6 外显子的丙氨酸 63 编码三联体中存在一个纯合的单核苷酸（A）缺失，该缺失不会立即导致氨基酸改变，但会导致 11 个氨基酸后出现一个终止密码子，从而导致肽的过早终止。这种 DNAJC19 蛋白位于线粒体内膜，被证明具有线粒体伴侣的功能。
这是首例 DCMA 综合征（人类 DNAJC19 缺乏症）的临床报告，与欧洲诊断的严重扩张型心肌病病例有关。DNAJC19 缺乏症导致尿液有机酸分析中出现相对特异的发现（甲基戊二酸尿症 V 型），结合随后的心脏疾病的临床特征，可以在进行分子遗传学分析之前进行有效的筛查。
