Phenotypic variability in a Tunisian family with X-linked adrenoleukodystrophy caused by the p.Gln316Pro novel mutation

• We identify a novel mutation c.947A > C in the ABCD1 gene in the two siblings.
• We demonstrate the phenotypic variability between two siblings in one family.
• Using Polyphen and SIFT software we demonstrate that new mutation is damaging.
• We performed a PCR-RFLP to identify healthy, homozygous and heterozygous individuals for this mutation.

IntroductionX-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.Patients and methodsThe present study reports the clinical, biochemical and molecular investigation in a Tunisian family with two affected males with childhood cerebral adrenoleukodystrophy.ResultsThe 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.ConclusionsBased on the disease's progress, the clinical signs and biochemical aspects between the two siblings, we demonstrate that there is no correlation genotype–phenotype.