Zhong Zilin, Zhou Zheng, Chen Jianjun, Zhang Jun
Birth Defect Group, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Regenerative Medicine, School of Medicine, Tongji University, Shanghai, China.
Front Genet. 2022 Jul 12;13:926511. doi: 10.3389/fgene.2022.926511. eCollection 2022.
OCA (oculocutaneous albinism) refers to a group of heterogeneous congenital disorders of which the common manifestations are variable degrees of cutaneous hypopigmentation and significant visual impairment, including poor visual acuity, photophobia, and nystagmus. Molecular analysis may elucidate its pathogenesis and be in favor of accurate diagnosis. High-throughput sequencing and Sanger sequencing were performed to detect mutational alleles and analysis was performed for prediction of variant pathogenicity. Ten -related and two -related patients were identified with 16 different variants with potential pathogenicity. Two novel missense variants [: c.623T > G, (Leu208Arg) and : c.1325A > G, (Asn442Ser)] are identified in this study, and three OCA cases are reported for the first time in Chinese population based on their associated variants. Analysis of crystal structures of TYR ortholog and its paralog TYRP1 suggests that the substitution of Leu may have an impact on protein stability. This study may facilitate OCA diagnosis by expanding the mutational spectrum of and as well as further basic studies about these two genes.
眼皮肤白化病（OCA）是一组异质性先天性疾病，其常见表现为不同程度的皮肤色素减退和严重的视力损害，包括视力差、畏光和眼球震颤。分子分析可能有助于阐明其发病机制并有利于准确诊断。进行了高通量测序和桑格测序以检测突变等位基因，并对变异致病性进行预测分析。鉴定出10例相关患者和2例相关患者，携带16种具有潜在致病性的不同变异。本研究鉴定出两个新的错义变异[: c.623T > G, (Leu208Arg) 和 : c.1325A > G, (Asn442Ser)]，并基于相关变异首次在中国人群中报道了3例OCA病例。对TYR直系同源物及其旁系同源物TYRP1的晶体结构分析表明，Leu的取代可能对蛋白质稳定性有影响。本研究通过扩大 和 基因的突变谱以及对这两个基因的进一步基础研究，可能有助于OCA的诊断。
