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SHR Neuro Cancer Cardio Lipid Metab Microb

Dohr, KA; Tokic, S; Gastager-Ehgartner, M; Stojakovic, T; Dumic, M; Plecko, B; Dumic, KK.
Two Single Nucleotide Deletions in the ABCD1 Gene Causing Distinct Phenotypes of X-Linked Adrenoleukodystrophy.
Int J Mol Sci. 2023; 24(6): 5957 Doi: 10.3390/ijms24065957 [OPEN ACCESS]
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Leading authors Med Uni Graz

Dohr Katrin Andrea

Tokic Silvija

Co-authors Med Uni Graz

Gastager-Ehgartner Magdalena

Plecko Barbara

Stojakovic Tatjana

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Abstract:

X-linked adrenoleukodystrophy (X-ALD) is a rare inborn error of the peroxisomal metabolism caused by pathologic variants in the ATP-binding cassette transporter type D, member 1 (ABCD1) gene located on the X-chromosome. ABCD1 protein, also known as adrenoleukodystrophy protein, is responsible for transport of the very long chain fatty acids (VLCFA) from cytoplasm into the peroxisomes. Therefore, altered function or lack of the ABCD1 protein leads to accumulation of VLCFA in various tissues and blood plasma leading to either rapidly progressive leukodystrophy (cerebral ALD), progressive adrenomyeloneuropathy (AMN), or isolated primary adrenal insufficiency (Addison's disease). We report two distinct single nucleotide deletions in the ABCD1 gene, c.253delC [p.Arg85Glyfs*18] in exon 1, leading to both cerebral ALD and to AMN phenotype in one family, and c.1275delA [p.Phe426Leufs*15] in exon 4, leading to AMN and primary adrenal insufficiency in a second family. For the latter variant, we demonstrate reduced mRNA expression and a complete absence of the ABCD1 protein in PBMC. Distinct mRNA and protein expression in the index patient and heterozygous carriers does not associate with VLCFA concentration in plasma, which is in line with the absence of genotype-phenotype correlation in X-ALD.

Find related publications in this database (Keywords)

X-linked adrenoleukodystrophy

adrenomyeloneuropathy

pathogenic variant

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