背景:眼皮肤白化病(OCA)是一组异质性遗传疾病,其特征是头发色素沉着减少或完全缺乏,皮肤,和眼睛。它与视力下降有关,眼球震颤,畏光,和斜视.OCA1型(OCA1)和2型(OCA2)是由酪氨酸酶(TYR)和OCA2基因突变引起的,这是大多数OCA案例的原因。本研究旨在鉴定18位中国西南先证者的OCA突变谱。
结果:我们使用针对皮肤病的小组对400多个基因进行了测序,包括23个基因(TYR,OCA2,AP3B1,BLOC1S3,BLOC1S6,C10orf11,DTNBP1,FRMD7,GPR143,HPS1,HPS3,HPS4,HPS5,HPS6,LYST,MC1R,MITF,MLPH,MYO5A,RAB27A,SLC24A5,SLC45A2,TYRP1)与综合征性和非综合征性白化病相关。目标小组应用于来自中国西南地区的18名患者,9例(50%)患者被诊断为OCA1,9例(50%)被诊断为OCA2.我们的数据表明,OCA1和OCA2,最常见的亚型,在中国西南地区可能有相同的患病率。总的来说,我们使用NGS技术从18例OCA病例中鉴定出TYR和OCA2中的26种变体,包括人类基因突变数据库专业(HGMD)中提出的24个变体和两个新变体,在TYR中c.559_560inCATTATTATGTGTCAAATTCCCC和在OCA2中c.1514T>C,以前没有报道过。根据美国医学遗传学和基因组学学院(ACMG)的分类,c.559_560inCATTATTATTATGTCAAATTATCCCC(第G190cfs*12)被归类为致病变体,和c.1514T>C(p。F505S)被评估为可能的致病变体。
结论:鉴定了两个新的变体,其将扩展TYR和OCA2的突变谱。本研究的结果可能对遗传咨询有影响,载体筛选,和疾病的临床管理。
BACKGROUND: Oculocutaneous albinism (OCA) is a group of heterogeneous genetic diseases characterized by a reduction or complete lack of pigmentation in the hair, skin, and eyes. It is associated with reduced visual acuity, nystagmus, photophobia, and strabismus. OCA type 1 (OCA1) and type 2 (OCA2) are caused by mutations in the tyrosinase (TYR) and OCA2 genes, which are responsible for most cases of OCA. The present study aimed to identify the mutational spectra of 18 southwest Chinese probands with OCA.
RESULTS: We used a skin disease-targeted panel to sequence more than 400 genes, including 23 genes (TYR, OCA2, AP3B1, BLOC1S3, BLOC1S6, C10orf11, DTNBP1, FRMD7, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, MC1R, MITF, MLPH, MYO5A, RAB27A, SLC24A5, SLC45A2, TYRP1) associated with syndromic and non-syndromic albinism. The targeted panel was applied to 18 patients from southwest
China, nine (50%) patients were diagnosed with OCA1, and nine (50%) were diagnosed with OCA2. Our data indicate that OCA1 and OCA2, the most common subtypes, probably have the same prevalence in southwest
China. In total, we identified 26 variants in TYR and OCA2 from 18 OCA cases using the NGS technology, including 24 variants presented in the Human Gene Mutation Database Professional (HGMD) and two novel variants, c.559_560insCATTATTATGTGTCAAATTATCCCC in TYR and c.1514 T > C in OCA2, which have not been previously reported. According to the American College of Medical Genetics and Genomics (ACMG) classification, c.559_560insCATTATTATGTGTCAAATTATCCCC (p.G190Cfs*12) is classified as a pathogenic variant, and c.1514 T > C (p.F505S) is evaluated as a likely pathogenic variant.
CONCLUSIONS: Two novel variants were identified which will expand the mutational spectra of TYR and OCA2. The results of the present study may have implications for genetic counseling, carrier screening, and clinical management of the disease.