First functional analysis of a novel splicing mutation in the B3GALTL gene by an ex vivo approach in Tunisian patients with typical Peters plus syndrome

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• 作者：Afif Ben Mahmoud ; Olfa Siala ; Riadh Ben Mansour ; Fatma Driss ; Siwar Baklouti-Gargouri ; Emna Mkaouar-Rebai ; Neila Belguith ; Faiza Fakhfakh
• 关键词：B3GALTL ; beta-1 ; 3-glucosyltransferase ; cDNA ; DNA complementary to RNA ; PTC ; premature translation stop codon ; mRNA ; messenger ribonucleic acid ; NMD ; nonsense-mediated mRNA decay ; PPS ; Peters plus syndrome ; DNA ; deoxyribonucleic acid ; B3GTL ; beta3-glycosyl
• 刊名：Gene
• 出版年：2013
• 出版时间：10 December, 2013
• 年：2013
• 卷：532
• 期：1
• 页码：13-17
• 全文大小：466 K

文摘

Peters plus syndrome is a rare recessive autosomal disorder comprising ocular anterior segment dysgenesis, short stature, hand abnormalities and distinctive facial features. It was related only to mutations in the B3GALTL gene in the 13q12.3 region. In this study, we undertook the first functional analysis of a novel c.597-2 A > G splicing mutation within the B3GALTL gene using an ex-vivo approach. The results showed a complete skipping of exon 8 in the B3GALTL cDNA, which altered the open reading frame of the mutant transcript and generated a PTC within exon 9. This finding potentially elicits the nonsense mRNA to degradation by NMD (nonsense-mediated mRNA decay). The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation to ex-vivo results. The findings confirmed the key role played by the B3GALTL gene in typical Peters-plus syndromes and the utility of mRNA analysis to understand the primary impacts of this mutation and the phenotype of the disease.