title: 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.
abstract: 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.
authors: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia. Electronic address: afifbenmahmoud@gmail.com.
authors: Afif
authors: A
authors: Ben Mahmoud
authors: Olfa
authors: O
authors: Siala
authors: Riadh Ben
authors: RB
authors: Mansour
authors: Fatma
authors: F
authors: Driss
authors: Siwar
authors: S
authors: Baklouti-Gargouri
authors: Emna
authors: E
authors: Mkaouar-Rebai
authors: Neila
authors: N
authors: Belguith
authors: Faiza
authors: F
authors: Fakhfakh
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D003198:Computer Simulation; D003315:Cornea / Q000002:abnormalities*; D005091:Exons; D005700:Galactosyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005964:Glucosyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics*; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay; D022821:RNA Splice Sites; D012326:RNA Splicing; D014416:Tunisia
chemical_list: D022821:RNA Splice Sites; C514116:B3GLCT protein, human; D005700:Galactosyltransferases; D005964:Glucosyltransferases
keywords: B3GALTL; B3GALTL gene; B3GTL; CD; CV; DNA; DNA complementary to RNA; DNase; ESE; Exon skipping; F; Functional analysis; G418; Geneticin; HSF; Ins; MMLV; Moloney Murine Leukemia Virus; NMD; PCR; PPS; PTC; Peters plus syndrome; PolyA; R; RPMI; RT-PCR; Roswell Park Memorial Institute; SR; TMR; WT; aa; amino acid(s); base pair(s); beta-1,3-glucosyltransferase; beta3-glycosyltransferase-like; bp; cDNA; catalytic domain; consensus value; dNTP; deoxyribonuclease; deoxyribonucleic acid; deoxyribonucleoside triphosphate; exonic splicing enhancer; forward; human splicing finder; insertion; mRNA; messenger ribonucleic acid; nonsense-mediated mRNA decay; polyadenylation; polymerase chain reaction; premature translation stop codon; reverse; reverse transcription polymerase chain reaction; splice site; ss; stem region; transmembrane region; wild type; β-galactosidase; βGal