Introduction: 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.
Patients and 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.
Keywords: ABCD1 gene; Addison disease; Childhood cerebral ALD; Novel mutation; Phenotypic variability; VLCFA; X-linked adrenoleukodystrophy.
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