Monica Penon-Portmann, Kendyl Naugle, Frank Brodie, Julie Schallhorn, Paul Griggs, Joyce So
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引用次数: 0
摘要
OPA3 基因的杂合突变与常染色体显性视神经萎缩-3(OPA3)有关,而双倍拷贝突变则导致常染色体隐性 3-甲基戊二酸尿症 III 型。迄今为止,所有出现 OPA3 基因致病变异的病例都表现为视神经萎缩。我们报告了一个患有先天性白内障、听力损失和神经病变的大家庭,该家族的血统中存在一个可能致病的 OPA3 新型错义变体,c.30G>C; p.(Lys10Asn) 与疾病分离。该家族的临床表现与之前报道的 OPA3 病例有明显的表型重叠,但明显缺乏视神经萎缩。对 OPA3 中所有已知的疾病相关变异进行分析后发现,与功能缺失变异相比,OPA3 表型患者中的错义变异更为丰富,而功能缺失变异更有可能在 3-甲基戊二酸尿症 III 型患者中出现,这支持了不同的疾病机制。该病例拓宽了与OPA3突变相关的临床和遗传谱,并强调视神经萎缩并非OPA3相关疾病的必然特征。
Novel heterozygous OPA3 variant in a family with congenital cataracts, sensorineural hearing loss and neuropathy, without optic atrophy and comparison of pathogenic and population variants.
Heterozygous mutations in the OPA3 gene are associated with autosomal dominant optic atrophy-3 (OPA3), whereas biallelic mutations cause autosomal recessive 3-methylglutaconic aciduria type III. To date, all cases with pathogenic variants in the gene OPA3 have presented with optic atrophy. We report a large family with congenital cataracts, hearing loss and neuropathy, with a likely pathogenic novel missense variant in OPA3, c.30G>C; p.(Lys10Asn) that segregates with disease in the family pedigree. The family's clinical presentation has significant phenotypic overlap with previously reported cases of OPA3, except for a notable lack of optic atrophy. The analysis of all known disease-associated variants in OPA3 revealed an enrichment in missense variants in patients with OPA3 phenotype compared with loss-of-function variants, which are more likely to be observed in individuals with 3-methylglutaconic aciduria type III, supporting different mechanisms of disease. This case broadens the clinical and genetic spectrum associated with OPA3 mutations and highlights that optic atrophy is not an obligate feature of OPA3-related disorders.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.