Transcriptomic Analysis of Identical Twins with Different Onset Ages of Adrenoleukodystrophy

Abstract

Adrenoleukodystrophy (ALD) is a rare X-linked neurogenetic disease caused by mutations in the ABCD1 gene. Currently, the molecular mechanisms underlying the onset and severity of ALD still remain unclear. Therefore, the aim of this paper is to mine information on candidate genes associated with onset and severity of ALD by transcriptome sequencing of whole blood samples from monozygotic twin families with ALD disease. The identifying of differentially expressed genes (DEGs), set theory analysis, gene enrichment analysis, and classification statistics of expression trend had been executed to identify potential candidate genes inducing the onset and severity of ALD in patients. And, eight ALD patients, which constituted by two normal children, two ALD child twins, twins’ mother, twins’ adult uncle with ALD, twins’ grandmother, and a normal adult had been used. In the present, five distinct sets of differentially expressed genes (DEGs) were identified via using whole blood samples from a family of identical twins with different onset ages and ABCD1 exon 2 deletion. Then, 39 DEGs of A∩B∩C-D and A∩B-D as well as 425 DEGs of C∩E had been considered as relating genes with the onset and severity of ALD. Especially, C4BPA, TPBG, CEP112, CHST15, SMAD1, IL-26, and LRRC69 had shown more important than others about ALD onset. Meanwhile, KEGG and GO enrichment further suggested the role of Ca 2+ homeostasis and plasma membrane for ALD onset and severity. Finally, expression pattern analysis further demonstrated the pivotal role of the selected DEG sets. The information on candidate genes of this research had been considered as the crucial for preliminarily exploring the molecular mechanisms relating to the onset and severity of ALD, which offered novel insights and research directions for mitigating and treating the development of ALD.