背景:眼皮肤白化病(OCA)是一组罕见的遗传性疾病,其特征是皮肤中黑色素减少或完全缺乏,头发,和眼睛。患者出现无色视网膜,淡粉色虹膜,和学生,和对光的恐惧。皮肤,眉毛,头发,和其他体毛是白色或黄白色。这些病症是由黑色素产生所必需的特定基因的突变引起的。OCA分为八种临床类型(OCA1-8),每个都有不同的临床表型和潜在的遗传因素。本研究旨在确定中国汉族家庭中非综合征性OCA的遗传原因。
方法:我们对家庭成员进行了全面的临床检查,使用全外显子组测序(WES)技术筛选突变位点,并使用计算机模拟工具预测突变。
结果:患者临床表现为白皮,黄色的头发,脸颊和鼻梁上有一些雀斑,视力下降,蓝色虹膜,定义不清的光盘边界,眼底色素沉着不足,和显著的血管暴露。WES测试结果表明该患者在OCA2基因中具有复合杂合突变(c.1258G>A(p。G420R),c.1441G>A(p。A481T),和c.2267-2A>C),分别,起源于她的父母。其中,c.1258G>A(p。G420R)是一种具有致病性的从头突变。我们的分析表明,OCA2基因中的复合杂合突变是该患者疾病的主要原因。
结论:WES等新一代测序技术在临床实践中的广泛应用,可以有效替代常规检测方法,更快速、准确地辅助临床疾病诊断。新发现的c.1258G>A(p。G420R)突变可以更新和扩展OCA2型白化病的基因突变谱。
BACKGROUND: Oculocutaneous albinism (OCA) is a group of rare genetic disorders characterized by a reduced or complete lack of melanin in the skin, hair, and eyes. Patients present with colorless retina, pale pink iris, and pupil, and fear of light. The skin, eyebrows, hair, and other body hair are white or yellowish-white. These conditions are caused by mutations in specific genes necessary for the production of melanin. OCA is divided into eight clinical types (OCA1-8), each with different clinical phenotypes and potential genetic factors. This study aimed to identify the genetic causes of non-syndromic OCA in a Chinese Han family.
METHODS: We performed a comprehensive clinical examination of family members, screened for mutation loci using whole exome sequencing (WES) technology, and predicted mutations using In silico tools.
RESULTS: The patient\'s clinical manifestations were white skin, yellow hair, a few freckles on the cheeks and bridge of the nose, decreased vision, blue iris, poorly defined optic disk borders, pigmentation of the fundus being insufficient, and significant vascular exposure. The WES test results indicate that the patient has compound heterozygous mutations in the OCA2 gene (c.1258G > A (p.G420R), c.1441G > A (p.A481T), and c.2267-2 A > C), respectively, originating from her parents. Among them, c.1258G > A (p.G420R) is a de novo mutation with pathogenic. Our analysis suggests that compound heterozygous mutations in the OCA2 gene are the primary cause of the disease in this patient.
CONCLUSIONS: The widespread application of next-generation sequencing technologies such as WES in clinical practice can effectively replace conventional detection methods and assist in the diagnosis of clinical diseases more quickly and accurately. The newly discovered c.1258G > A (p.G420R) mutation can update and expand the gene mutation spectrum of OCA2-type albinism.