Bastaki Fatma, Mohamed Madiha, Nair Pratibha, Saif Fatima, Mustafa Ethar M, Bizzari Sami, Al-Ali Mahmoud T, Hamzeh Abdul Rezzak
Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, UAE.
Centre for Arab Genomic Studies, Dubai, UAE.
Int J Dermatol. 2017 May;56(5):514-523. doi: 10.1111/ijd.13568. Epub 2017 Feb 24.
Clinical and molecular heterogeneity is a prominent characteristic of congenital ichthyoses, with the involvement of numerous causative loci. Mutations in these loci feature in autosomal recessive congenital ichthyoses (ARCIs) quite variably, with certain genes/mutations being more frequently uncovered in particular populations.
In this study, we used whole exome sequencing as well as direct Sanger sequencing to uncover four novel mutations in ARCI-related genes, which were found in families from the United Arab Emirates. In silico tools such as CADD and SIFT Indel were used to predict the functional consequences of these mutations.
The here-presented mutations occurred in three genes (ALOX12B, TGM1, ABCA12), and these are a mixture of missense and indel variants with damaging functional consequences on their encoded proteins.
This study presents an overview of the mutations that were found in ARCI-related genes in Arabs and discusses molecular and clinical details pertaining to the above-mentioned Emirati cases and their novel mutations with special emphasis on the resulting protein changes.
临床和分子异质性是先天性鱼鳞病的一个突出特征，涉及众多致病基因座。这些基因座中的突变在常染色体隐性先天性鱼鳞病（ARCI）中表现差异很大，某些基因/突变在特定人群中更常被发现。
在本研究中，我们使用全外显子组测序以及直接桑格测序法，在来自阿拉伯联合酋长国的家庭中发现了4个ARCI相关基因的新突变。利用诸如CADD和SIFT Indel等电子工具来预测这些突变的功能后果。
此处呈现的突变发生在3个基因（ALOX12B、TGM1、ABCA12）中，这些是错义突变和插入缺失变异的混合，对其编码的蛋白质具有有害的功能影响。
本研究概述了在阿拉伯人中发现的ARCI相关基因的突变情况，并讨论了与上述阿联酋病例及其新突变相关的分子和临床细节，特别强调了由此导致的蛋白质变化。
