Molecular characterization of a series of 990 index patients with albinism
Molecular characterization of a series of 990 index patients with albinism
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DOI：
10.1111/pcmr.12688
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发表时间：
2018-07-01
影响因子：
4.3
通讯作者：
Arveiler, Benoit
中科院分区：
文献类型：
--
作者：
Lasseaux, Eulalie;Plaisant, Claudio;Arveiler, Benoit
白化病是一种临床和遗传异质性疾病，以不同程度的色素沉着、眼球震颤、中央凹发育不全和视神经交叉走错为特征。广泛的表型异质性阻碍了表型-基因型相关性的建立。为了获得准确的诊断，我们使用靶向下一代测序（NGS）和高分辨率比较基因组杂交技术筛选了990例白化病患者的19个已知白化病基因。72.32%的患者获得分子诊断。共鉴定出243个新的致病变异。基因内重排占所有致病等位基因的10.8%。NGS小组分析允许对最罕见的疾病形式进行诊断，否则无法诊断。由于不同形式的疾病的临床重叠，目前的诊断显然依赖于分子基础。
Albinism is a clinically and genetically heterogeneous disease characterized by variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity impedes the establishment of phenotype-genotype correlations. To obtain a precise diagnosis, we screened the 19 known albinism genes in 990 index patients using targeted next-generation sequencing (NGS) and high-resolution comparative genomic hybridization. A molecular diagnosis was obtained in 72.32% of patients. A total of 243 new pathogenic variants were identified. Intragenic rearrangements represented 10.8% of all pathogenic alleles. NGS panel analysis allowed establishing a diagnosis for the rarest forms of the disease, which could not be diagnosed otherwise. Because of the clinical overlap between the different forms of the disease, diagnosis nowadays clearly relies on molecular grounds.