title: Phenotypic variability in a Tunisian family with X-linked adrenoleukodystrophy caused by the p.Gln316Pro novel mutation.
abstract: BACKGROUND
  X-linked adrenoleukodystrophy is a neurodegenerative recessive disorder that affects the brain white matter and associated with adrenal insufficiency. It is characterized by an abnormal function of the peroxisomes, which leads to an accumulation of the 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. Mutations in the ABCD1 gene affect the function of the encoded protein ALDP, an ATP-binding cassette transporter located in the peroxisomal membrane protein.
  
  
  METHODS
  The present study reports the clinical, biochemical and molecular investigation in a Tunisian family with two affected males with childhood cerebral adrenoleukodystrophy.
  
  
  RESULTS
  The ABCD1 gene sequencing indicated a novel hemizygous missense mutation c.947A>C (p.Gln316Pro) in the exon 2 of the ABCD1 gene in the patients, their mother and their sisters. This missense variation was predicted to be possibly damaging by the PolyPhen and SIFT prediction software. Although presence of the same mutation c.947A>C in both siblings, they present different clinical signs.
  
  
  CONCLUSIONS
  Based on the disease's progress, the clinical signs and biochemical aspects between the two siblings, we demonstrate that there is no correlation genotype-phenotype.
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia. Electronic address: fakhrikallabi@yahoo.fr.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Kallabi
authors.affiliation: Service of Neuropaediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Emna
authors.initials: E
authors.lastname: Ellouz
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Tabebi
authors.affiliation: Uniazah Pharmacy College, Qassim University, Alqassim, Saudi Arabia.
authors.forename: Ghada
authors.initials: G
authors.lastname: Ben Salah
authors.affiliation: Service of biochemistry, C.H.U. La Rabta, Tunis, Tunisia.
authors.forename: Naziha
authors.initials: N
authors.lastname: Kaabechi
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Keskes
authors.affiliation: Service of Neuropaediatrics, C.H.U. Hedi Chaker, Sfax, Tunisia.
authors.forename: Chahnez
authors.initials: C
authors.lastname: Triki
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia; Service of Medical Genetics, C.H.U Hedi Chaker, Sfax, Tunisia. Electronic address: hassen.kamoun@yahoo.fr.
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*; D000326:Adrenoleukodystrophy / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D035781:Siblings; 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; Addison disease; Childhood cerebral ALD; Novel mutation; Phenotypic variability; VLCFA; X-linked adrenoleukodystrophy