title: Molecular characterization of X-linked adrenoleukodystrophy in a Tunisian family: identification of a novel missense mutation in the ABCD1 gene.
abstract: BACKGROUND
  X-linked adrenoleukodystrophy (X-ALD) is a recessive neurodegenerative disorder that affects the brain's white matter and is associated with adrenal insufficiency. It is characterized by an abnormal function of the peroxisomes, which leads to an accumulation of very long-chain fatty acids (VLCFA) in plasma and tissues, especially in the cortex of the adrenal glands and the white matter of the central nervous system, causing demyelinating disease and adrenocortical insufficiency (Addison's disease). X-ALD is caused by a mutation in the ABCD1 gene (ATP-binding cassette, subfamily D, member 1), which encodes the adrenoleukodystrophy protein involved in the transport of fatty acids into the peroxisome for degradation.
  
  
  OBJECTIVE
  We report here a disease-related variant in the ABCD1 gene in a 19-year-old Tunisian boy with childhood cerebral adrenoleukodystrophy.
  
  
  METHODS
  The diagnosis was based on clinical symptoms, high levels of VLCFA in plasma, typical MRI pattern and molecular analysis.
  
  
  RESULTS
  Molecular analysis by direct sequencing of the ABCD1 gene showed the presence of a novel missense mutation c.284C>A (p.Ala95Asp) occurring in the transmembrane domain in the proband, his mother and his sister.
  
  
  CONCLUSIONS
  Using bioinformatic tools we suggest that this novel variant may have deleterious effects on adrenoleukodystrophy protein structure and function.
authors: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Sfax, Tunisia.
authors: Fakhri
authors: F
authors: Kallabi
authors: Ikhlass
authors: I
authors: Hadj Salem
authors: Ghada
authors: G
authors: Ben Salah
authors: Hadhami
authors: H
authors: Ben Turkia
authors: Amel
authors: A
authors: Ben Chehida
authors: Neji
authors: N
authors: Tebib
authors: Faiza
authors: F
authors: Fakhfakh
authors: Hassen
authors: H
authors: Kamoun
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000097:blood / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005192:Family Health; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D020539:Sequence Analysis, Protein; D014416:Tunisia; D055815:Young Adult
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D005227:Fatty Acids