Abstract：
Recently, Stenton et al. (2021) described a new, autosomal recessive inheritance pattern of Leber\'s hereditary optic neuropathy (LHON) caused by missense variants in the DNAJC30 gene. The DNAJC30 c.152A > G, p.(Tyr51Cys) variant was by far the most common variant reported in patients originating from Eastern Europe, therefore, it is believed to be a founder variant in these populations. We report the first two cases of DNAJC30-linked autosomal recessive LHON in a young male and a female originating from Estonia. The patients presented severe loss of central vision and clinical features indistinguishable from mitochondrial LHON. The whole exome sequencing carried out in the male patient and the next-generation sequencing panel in the young female patient identified the same homozygous missense variant in the DNAJC30 gene. Our cases further reinforce the pathogenicity of c.152A > G, p.(Tyr51Cys) DNAJC30 variant causing autosomal recessive LHON. According to the gnomAD database, the allele frequency of this variant in the Estonian population is 0.8%, translating into a prevalence of carriers of 1:60. It is the highest among different gnomAD populations. Applying the Hardy-Weinberg equation, an estimated 92 persons in the Estonian population carry the homozygous variant c.152A > G, p.(Tyr51Cys) in DNAJC30. In patients with LHON, we advise sequencing both the DNAJC30 gene and mitochondrial DNA simultaneously.
摘要：
最近,Stenton等人。(2021)描述了一个新的，由DNAJC30基因错义变异引起的Leber遗传性视神经病变(LHON)的常染色体隐性遗传模式。DNAJC30c.152A>G，p。（Tyr51Cys）变异是迄今为止在来自东欧的患者中报道的最常见的变异，因此,它被认为是这些人群中的创始人变体。我们报告了起源于爱沙尼亚的年轻男性和女性中DNAJC30连锁常染色体隐性LHON的前两例。患者表现出严重的中央视力丧失和临床特征，与线粒体LHON无法区分。在男性患者中进行的整个外显子组测序和在年轻女性患者中进行的下一代测序小组鉴定了DNAJC30基因中的相同纯合错义变体。我们的病例进一步加强了c.152A>G的致病性，p。（Tyr51Cys）DNAJC30变异导致常染色体隐性LHON。根据gnomAD数据库,这种变异在爱沙尼亚人群中的等位基因频率为0.8%，转化为1:60的携带者患病率。在不同的gnomAD种群中最高。应用Hardy-Weinberg方程,爱沙尼亚人口中估计有92人携带纯合变体c.152A>G，p.（Tyr51Cys）在DNAJC30。在患有LHON的患者中，我们建议同时对DNAJC30基因和线粒体DNA进行测序.
