Kazmierczak de Camargo João Paulo, Prezia Giovanna Nazaré de Barros, Shiokawa Naoye, Sato Mario Teruo, Rosati Roberto, Beate Winter Boldt Angelica
Post-Graduation Program in Genetics, Department of Genetics, Federal University of Paraná, Curitiba, Brazil.
Post-Graduation Program in Biotechnology Applied to Child and Adolescent Health, Faculdades Pequeno Príncipe and Pelé Pequeno Príncipe Research Institute, Curitiba, Brazil.
Front Genet. 2022 May 17;13:886461. doi: 10.3389/fgene.2022.886461. eCollection 2022.
Central areolar choroidal dystrophy (CACD) is a rare hereditary disease that mainly affects the macula, resulting in progressive and usually profound visual loss. Being part of congenital retinal dystrophies, it may have an autosomal dominant or recessive inheritance and, until now, has no effective treatment. Given the shortage of genotypic information about the disease, this work systematically reviews the literature for CACD-causing genes. Three independent researchers selected 33 articles after carefully searching and filtering the Scielo, Pubmed, Lilacs, Web of Science, Scopus, and Embase databases. Mutations of six genes (, and ) are implicated in the monogenic dominant inheritance of CACD. They are functionally related to photoreceptors (either in the phototransduction process, as in the case of , or the recovery of retinal photodegradation in photoreceptors for or the formation and maintenance of specific structures within photoreceptors for ). The identified genetic variants do not explain all observed clinical features, calling for further whole-genome and functional studies for this disease. A network analysis with the CACD-related genes identified in the systematic review resulted in the identification of another 20 genes that may influence CACD onset and symptoms. Furthermore, an enrichment analysis allowed the identification of 13 transcription factors and 4 long noncoding RNAs interacting with the products of the previously mentioned genes. If mutated or dysregulated, they may be directly involved in CACD development and related disorders. More than half of the genes identified by bioinformatic tools do not appear in commercial gene panels, calling for more studies about their role in the maintenance of the retina and phototransduction process, as well as for a timely update of these gene panels.
中心性晕轮状脉络膜营养不良（CACD）是一种罕见的遗传性疾病，主要影响黄斑区，导致进行性且通常严重的视力丧失。作为先天性视网膜营养不良的一部分，它可能具有常染色体显性或隐性遗传，并且迄今为止尚无有效的治疗方法。鉴于有关该疾病的基因型信息匮乏，本研究系统地回顾了导致CACD的相关基因的文献。三名独立研究人员在仔细搜索和筛选了Scielo、Pubmed、Lilacs、Web of Science、Scopus和Embase数据库后，挑选出33篇文章。六个基因（，和）的突变与CACD的单基因显性遗传有关。它们在功能上与光感受器相关（要么参与光转导过程，如的情况，要么参与光感受器中视网膜光降解的恢复，如或参与光感受器内特定结构的形成和维持，如）。所鉴定的基因变异并不能解释所有观察到的临床特征，这就需要对该疾病进行进一步的全基因组和功能研究。对在系统评价中鉴定出的与CACD相关的基因进行网络分析，又鉴定出另外20个可能影响CACD发病和症状的基因。此外，富集分析还鉴定出13个转录因子和4个与上述基因产物相互作用的长链非编码RNA。如果这些基因发生突变或失调，它们可能直接参与CACD的发展和相关疾病。通过生物信息学工具鉴定出的基因中，超过一半未出现在商业基因检测板中，这就需要对它们在维持视网膜和光转导过程中的作用进行更多研究，并及时更新这些基因检测板。
