Khordadpoor-Deilamani Faravareh, Akbari Mohammad Taghi, Karimipoor Morteza, Javadi Gholam Reza
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
J Hum Genet. 2016 May;61(5):373-9. doi: 10.1038/jhg.2015.167. Epub 2016 Jan 28.
Albinism is a heterogeneous genetic disorder of melanin synthesis that results in hypopigmented hair, skin and eyes. It is associated with decreased visual acuity, nystagmus, strabismus and photophobia. Six genes are known to be involved in nonsyndromic oculocutaneous albinism (OCA). In this study, we aimed to find the disease causing mutations in albinism patients using homozygosity mapping. Twenty three unrelated patients with nonsyndromic OCA or autosomal recessive ocular albinism were recruited in this study. All of the patients' parents had consanguineous marriage and all were screened for TYR mutations previously. At first, we performed homozygosity mapping using fluorescently labeled primers to amplify a novel panel of 13 STR markers inside the OCA genes and then the screened loci in each family were studied using PCR and cycle sequencing methods. We found five mutations including three mutations in OCA2, one mutation in SLC45A2 and one mutation in C10ORF11 genes, all of which were novel. In cases where the disease causing mutations are identical by descent due to a common ancestor, these STR markers can enable us to screen for the responsible genes.
白化病是一种黑色素合成的异质性遗传疾病,会导致毛发、皮肤和眼睛色素减退。它与视力下降、眼球震颤、斜视和畏光有关。已知有六个基因参与非综合征性眼皮肤白化病(OCA)。在本研究中,我们旨在使用纯合性定位来寻找白化病患者中导致疾病的突变。本研究招募了23名非综合征性OCA或常染色体隐性眼白化病的无关患者。所有患者的父母均为近亲结婚,且之前都接受了酪氨酸酶(TYR)突变筛查。首先,我们使用荧光标记引物进行纯合性定位,以扩增OCA基因内一组新的13个短串联重复序列(STR)标记,然后使用聚合酶链反应(PCR)和循环测序方法研究每个家族中筛选出的位点。我们发现了五个突变,包括OCA2基因中的三个突变、SLC45A2基因中的一个突变和C10ORF11基因中的一个突变,所有这些突变都是新发现的。在由于共同祖先而导致致病突变同源的情况下,这些STR标记可以使我们筛选出致病基因。