Molecular basis of albinism in India: Evaluation of seven potential candidate genes and some new findings
Molecular basis of albinism in India: Evaluation of seven potential candidate genes and some new findings
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DOI：
10.1016/j.gene.2012.09.012
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发表时间：
2012-12-15
期刊：
影响因子：
3.5
通讯作者：
Ray, K.
中科院分区：
文献类型：
--
作者：
Mondal, M.;Sengupta, M.;Ray, K.
白化病是一组遗传性疾病，具有取决于患者遗传背景的广谱低色素表型。眼皮肤白化病（OCA）患者的眼睛，皮肤和头发中几乎没有色素，而眼白化病（OA）主要表现为眼部症状，皮肤和头发的颜色可能从接近正常到非常公平。直接或间接调节黑色素产生的基因突变导致不同形式的白化病，其临床特征重叠。在这项研究中，来自24个家庭的27个白化病个体通过PCR测序为基础的方法筛选致病变异。TYR、OCA 2、TYRP 1、SLC 45 A2、SLC 24 A5、TYRP 2和SILV基因被选为候选基因。我们在8例无关患者中发现了5个TYR和3个OCA 2突变，大多数为纯合子状态，其中包括一例常染色体隐性遗传性眼白化病（AROA）。一个纯合的4-核苷酸新插入SLC 24 A5中检测到一个极端的皮肤色素减退的人。在一名患者的TYRP 2基因中发现了一种潜在的致病变异。单倍型分析在经典的OCA基因携带纯合突变的患者建议创始人效应。这是印度AROA患者携带OCA 2突变的第一份报告。我们的研究结果还首次揭示了SLC 24 A5的突变可能导致人类的极端色素减退。(C)2012爱思唯尔有限公司版权所有。
Albinism represents a group of genetic disorders with a broad spectrum of hypopigmentary phenotypes dependent on the genetic background of the patients. Oculocutaneous albinism (OCA) patients have little or no pigment in their eyes, skin and hair, whereas ocular albinism (OA) primarily presents the ocular symptoms, and the skin and hair color may vary from near normal to very fair. Mutations in genes directly or indirectly regulating melanin production are responsible for different forms of albinism with overlapping clinical features. In this study, 27 albinistic individuals from 24 families were screened for causal variants by a PCR-sequencing based approach. TYR, OCA2, TYRP1, SLC45A2, SLC24A5, TYRP2 and SILV were selected as candidate genes. We identified 5 TYR and 3 OCA2 mutations, majority in homozygous state, in 8 unrelated patients including a case of autosomal recessive ocular albinism (AROA). A homozygous 4-nucleotide novel insertion in SLC24A5 was detected in a person showing with extreme cutaneous hypopigmentation. A potential causal variant was identified in the TYRP2 gene in a single patient. Haplotype analyses in the patients carrying homozygous mutations in the classical OCA genes suggested founder effect. This is the first report of an Indian AROA patient harboring a mutation in OCA2. Our results also reveal for the first time that mutations in SLC24A5 could contribute to extreme hypopigmentation in humans. (C) 2012 Elsevier B.V. All rights reserved.