Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
College of Osteopathic Medicine, Des Moines University, Des Moines, IA 50312, USA.
Genes (Basel). 2022 Jun 2;13(6):1005. doi: 10.3390/genes13061005.
Dominant optic atrophy (DOA), MIM # 605290, is the most common hereditary optic neuropathy inherited in an autosomal dominant pattern. Clinically, it presents a progressive decrease in vision, central visual field defects, and retinal ganglion cell loss. A biallelic mode of inheritance causes syndromic DOA or Behr phenotype, MIM # 605290. This case report details a family with Biallelic Optic Atrophy 1 (OPA1). The proband is a child with a severe phenotype and two variants in the OPA1 gene. He presented with congenital nystagmus, progressive vision loss, and optic atrophy, as well as progressive ataxia, and was found to have two likely pathogenic variants in his OPA1 gene: c.2287del (p.Ser763Valfs*15) maternally inherited and c.1311A>G (p.lIle437Met) paternally inherited. The first variant is predicted to be pathogenic and likely to cause DOA. In contrast, the second is considered asymptomatic by itself but has been reported in patients with DOA phenotype and is presumed to act as a phenotypic modifier. On follow-up, he developed profound vision impairment, intractable seizures, and metabolic strokes. A literature review of reported biallelic OPA1-related Behr syndrome was performed. Twenty-one cases have been previously reported. All share an early-onset, severe ocular phenotype and systemic features, which seem to be the hallmark of the disease.
显性视神经萎缩（DOA），MIM #605290，是最常见的常染色体显性遗传视神经病变。临床上表现为视力进行性下降、中心视野缺损和视网膜神经节细胞丢失。双等位基因突变导致综合征性 DOA 或 Behr 表型，MIM #605290。本病例报告详细介绍了一个具有双等位基因视神经萎缩 1 型（OPA1）的家族。先证者是一名儿童，表现为严重表型，OPA1 基因有两个变异。他患有先天性眼球震颤、进行性视力丧失和视神经萎缩，以及进行性共济失调，并在 OPA1 基因中发现了两个可能的致病变异：c.2287del（p.Ser763Valfs*15）母系遗传和 c.1311A>G（p.lIle437Met）父系遗传。第一个变异被预测为致病性的，很可能导致 DOA。相比之下，第二个变异本身被认为是无症状的，但已在具有 DOA 表型的患者中报道，被认为是表型修饰剂。随访时，他出现了严重的视力损害、难治性癫痫和代谢性中风。对报告的双等位基因 OPA1 相关 Behr 综合征进行了文献复习。以前已经报告了 21 例。所有病例均具有早发性、严重的眼部表型和全身特征，这似乎是该疾病的标志。
