Medical Genetics Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
Gene. 2014 Jan 1;533(1):398-402. doi: 10.1016/j.gene.2013.09.053. Epub 2013 Oct 3.
Oculocutaneous Albinism (OCA) is a heterogeneous group of inherited diseases involving hair, skin and eyes. To date, six forms are recognized on the effects of different melanogenesis genes. OCA4 is caused by mutations in SLC45A2 showing a heterogeneous phenotype ranging from white hair, blue irides and nystagmus to brown/black hair, brown irides and no nystagmus. The high clinic variety often leads to misdiagnosis. Our aim is to contribute to OCA4 diagnosis defining SLC45A2 genetic variants in Italian patients with OCA without any TYR, OCA2 and TYRP1 gene defects.
After the clinical diagnosis of OCA, all patients received genetic counseling and genetic test. Automatic sequencing of TYR, OCA2, and TYRP1 genes was performed on DNA of 117 albino patients. Multiplex Ligation-dependent Probe Amplification (MLPA) was carried out on TYR and OCA2 genes to increase the mutation rate. SLC45A2 gene sequencing was then executed in the patients with a single mutation in one of the TYR, OCA2, TYRP1 genes and in the patients, which resulted negative at the screening of these genes.
SLC45A2 gene analysis was performed in 41 patients and gene alterations were found in 5 patients. Four previously reported SLC45A2 mutations were found: p.G100S, p.W202C, p.A511E and c.986delC, and three novel variants were identified: p.M265L, p.H94D, and c.1156+1G>A. All the alterations have been detected in the group of patients without mutations in the other OCA genes.
Three new variants were identified in OCA4 gene; the analysis allowed the classification of a patient previously misdiagnosed as OA1 because of skin and hair pigmentation presence. The molecular defects in SLC45A2 gene represent the 3.4% in this cohort of Italian patients, similar to other Caucasian populations; our data differ from those previously published by an Italian researcher group, obtained on a smaller cohort of patients.
眼皮肤白化病（OCA）是一组涉及毛发、皮肤和眼睛的遗传性疾病。迄今为止，已经在不同的黑色素生成基因的作用下识别出六种形式。OCA4 是由 SLC45A2 基因突变引起的，表现出从白发、蓝虹膜和眼球震颤到棕/黑头发、棕虹膜和无眼球震颤的异质性表型。临床表现的高度多样性常常导致误诊。我们的目的是通过对意大利无 TYR、OCA2 和 TYRP1 基因突变的 OCA 患者的 SLC45A2 基因变异进行研究，为 OCA4 的诊断做出贡献。
在临床诊断为 OCA 后，所有患者均接受遗传咨询和基因检测。对 117 名白化病患者的 DNA 进行 TYR、OCA2 和 TYRP1 基因的自动测序。对 TYR 和 OCA2 基因进行多重连接依赖性探针扩增（MLPA）以提高突变率。然后对在 TYR、OCA2、TYRP1 基因中的一个基因中存在单一突变的患者以及在这些基因筛查中呈阴性的患者进行 SLC45A2 基因测序。
对 41 名患者进行了 SLC45A2 基因分析，发现 5 名患者存在基因改变。发现了 4 种先前报道的 SLC45A2 突变：p.G100S、p.W202C、p.A511E 和 c.986delC，以及 3 种新的变体：p.M265L、p.H94D 和 c.1156+1G>A。所有这些改变均在其他 OCA 基因无突变的患者组中检测到。
在 OCA4 基因中发现了 3 种新的变体；该分析使一位先前因皮肤和头发色素沉着而误诊为 OA1 的患者得到了分类。SLC45A2 基因突变分析在意大利患者中的发生率为 3.4%，与其他白种人群相似；我们的数据与意大利研究小组以前发表的结果不同，该小组的研究对象数量较少。
