National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan.
Eur J Dermatol. 2012 Mar-Apr;22(2):178-81. doi: 10.1684/ejd.2011.1638.
A Mutations in the gene encoding the ABCA12 protein are associated with different subtypes of autosomal recessive congenital ichthyosis (ARCI), including Harlequin ichthyosis (HI), lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE). Disruption of ABCA12 lead to perturbed lipid transport in lamellar granules and a defective intercellular lipid layer of the stratum corneum. We have identified a large consanguineous Pakistani family affected by NCIE. Autozygosity mapping showed that affected individuals are homozygous for the ABCA12 gene region. Subsequent mutation screening revealed a homozygous c.4676G>T transition in all five affected family members. The mutation results in a novel p.G1559V substitution within the first nucleotide binding domain of ABCA12. The combined results support that an ABCA12 missense mutation, despite its location in a functional domain, may be associated with a mild ichthyosis phenotype. Furthermore, our findings increase the mutational spectrum in ABCA12 associated with ARCI of diagnostic and prognostic importance.
ABCA12 蛋白基因中的突变与常染色体隐性先天性鱼鳞病（ARCI）的不同亚型有关，包括丑角鱼鳞病（HI）、板层状鱼鳞病（LI）和非大疱性先天性鱼鳞病样红皮病（NCIE）。ABCA12 的破坏导致板层颗粒中的脂质转运紊乱和角质层细胞间脂质层的缺陷。我们已经确定了一个受 NCIE 影响的大型巴基斯坦近亲家族。自交系作图表明，受影响的个体在 ABCA12 基因区域是纯合子的。随后的突变筛选显示，所有 5 名受影响的家族成员均为纯合 c.4676G>T 转换。该突变导致 ABCA12 第一个核苷酸结合域内的新型 p.G1559V 取代。综合结果支持 ABCA12 的错义突变，尽管其位于功能域内，但可能与轻度鱼鳞病表型有关。此外，我们的发现增加了与 ARCI 相关的 ABCA12 突变的突变谱，这对诊断和预后具有重要意义。
