title: A de-novo large deletion of 2.8 kb produced in the ABCD1 gene causing adrenoleukodystrophy disease.
abstract: X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene, which encodes an ATP-binding cassette transporter protein, ALDP. The disease is characterized by increased concentrations of very long chain fatty acids (VLCFAs) in plasma, adrenal, testicular, and nerve tissues. For this study, our objective was to conduct clinical, molecular, and genetic studies of a Tunisian patient with X-ALD. The diagnosis was based on clinical indications, biochemical analyses, typical brain-scan patterns, and molecular biology; the molecular analyses were based on PCR, long-range PCR, and sequencing. The molecular analysis by long-range PCR and direct sequencing of the ABCD1 gene showed the presence of a de-novo 2794 bp deletion covering the whole of exon 2. Using bioinformatics tools, we demonstrate that the large deletion is located in a region rich with Alu sequences. Furthermore, we suggest that the AluJb sequence could be the cause of the large deletion of intron 1, exon 2, and intron 2, and the creation of a premature stop codon within exon 3. This report is the first report in which we demonstrate the breakpoints and the size of a large deletion in a Tunisian with X-ALD.
authors.affiliation: a Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, Road Majida Boulila, 3029 Sfax, Tunisia.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Kallabi
authors.affiliation: b Unaizah Pharmacy College, Qassim University, Saudi Arabia.
authors.forename: Ghada
authors.initials: G
authors.lastname: Ben Salah
authors.affiliation: c Service of Pediatrics, Rabta Hospital of Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Ben Chehida
authors.affiliation: a Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, Road Majida Boulila, 3029 Sfax, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Tabebi
authors.affiliation: a Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, Road Majida Boulila, 3029 Sfax, Tunisia.
authors.forename: Rahma
authors.initials: R
authors.lastname: Felhi
authors.affiliation: c Service of Pediatrics, Rabta Hospital of Tunis, Tunisia.
authors.forename: Hadhami
authors.initials: H
authors.lastname: Ben Turkia
authors.affiliation: c Service of Pediatrics, Rabta Hospital of Tunis, Tunisia.
authors.forename: Neji
authors.initials: N
authors.lastname: Tebib
authors.affiliation: a Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, Road Majida Boulila, 3029 Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Keskes
authors.affiliation: a Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, Road Majida Boulila, 3029 Sfax, Tunisia.|d Service of Medical Genetics, Hedi Chaker Hospital of 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 / Q000209:etiology / Q000235:genetics*; D018388:Codon, Terminator; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D018388:Codon, Terminator
keywords: ABCD1 gene; AluJb sequence; SINE sequences; X-adrenoleucodystrophy; adrénoleucodystrophie liée au chromosome X; gène ABCD1; large deletion; longue délétion; séquence AluJb; séquences SINE