title: Splicing defects in ABCD1 gene leading to both exon skipping and partial intron retention in X-linked adrenoleukodystrophy Tunisian patient.
abstract: X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encodes a peroxisomal membrane protein: the adrenoleukodystrophy protein. The disease is characterized by high concentrations of very long-chain fatty acids in plasma, adrenal, testicular and nervous tissues. Various types of mutations have been identified in the ABCD1 gene: point mutations, insertions, and deletions. To date, more than 40 point mutations have been reported at the splice junctions of the ABCD1 gene; only few functional studies have been performed to explore these types of mutations. In this study, we have identified de novo splice site mutation c.1780+2T>G in ABCD1 gene in an X-ALD Tunisian patient. Sequencing analysis of cDNA showed a minor transcript lacking exon 7 and a major transcript with a partial intron 7 retention due to activation of a new intronic cryptic splice site. Both outcomes lead to frameshifts with premature stop codon generation in exon 8 and intron 7 respectively. To the best of our knowledge, the current study demonstrates that a single splicing mutation affects the ABCD1 transcripts and the ALDP protein function.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia. Electronic address: fakhrikallabi@yahoo.fr.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Kallabi
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia.
authors.forename: Ikhlass
authors.initials: I
authors.lastname: Hadj Salem
authors.affiliation: Service de Pédiatrie, Hôpital La Rabta de Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Ben Chehida
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia.
authors.forename: Ghada
authors.initials: G
authors.lastname: Ben Salah
authors.affiliation: Service de Pédiatrie, Hôpital La Rabta de Tunis, Tunisia.
authors.forename: Hadhami
authors.initials: H
authors.lastname: Ben Turkia
authors.affiliation: Service de Pédiatrie, Hôpital La Rabta de Tunis, Tunisia.
authors.forename: Neji
authors.initials: N
authors.lastname: Tebib
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Keskes
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia; Service de Génétique Médicale, Hôpital Hédi Chaker Sfax, Tunisia.
authors.forename: Hassen
authors.initials: H
authors.lastname: Kamoun
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D005091:Exons; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D014416:Tunisia
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters
keywords: ABCD1 gene; Adrenal insufficiency; Exon skipping; Intron retention; X-ALD; mRNA splicing