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01-07-2008 | Original Article

A family with combined mutations of the hemophilia A and X-linked adrenoleukodystrophy genes

Authors: Brent L. Fogel, Pari Young, Arthur R. Thompson, Susan Perlman

Published in: Neurogenetics | Issue 3/2008

Abstract

X-linked adrenoleukodystrophy and hemophilia A are two distinct, potentially devastating, genetic diseases whose corresponding genes are located in close proximity on the X chromosome. Here we report a family with members affected with both conditions, only the second such family ever reported. Although a structural genomic rearrangement involving both genes was initially predicted to underlie this extremely rare phenotype, genotyping revealed the unlikely occurrence of two individual point mutations. Given the impact of this result on the heritability of the two disorders within the family, this case illustrates the significance of performing detailed molecular analysis in patients with multiple genetic disorders.

Moser HW, Mahmood A, Raymond GV (2007) X-linked adrenoleukodystrophy. Nat Clin Pract Neurol 3(3):140–151CrossRefPubMed

Moser HW, Raymond GV, Dubey P (2005) Adrenoleukodystrophy: new approaches to a neurodegenerative disease. JAMA 294(24):3131–3134CrossRefPubMed

Spurek M, Taylor-Gjevre R, Van Uum S et al (2004) Adrenomyeloneuropathy as a cause of primary adrenal insufficiency and spastic paraparesis. CMAJ 171(9):1073–1077CrossRefPubMedPubMedCentral

Moser H, Dubey P, Fatemi A (2004) Progress in X-linked adrenoleukodystrophy. Curr Opin Neurol 17(3):263–269CrossRefPubMed

Schiffman R, van der Knaap MS (2004) The latest on leukodystrophies. Curr Opin Neurol 17(2):187–192CrossRef

Kemp S, Pujol A, Waterham HR et al (2001) ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum Mutat 18(6):499–515CrossRefPubMed

Oldenburg J, Ananyeva NM, Saenko EL (2004) Molecular basis of haemophilia A. Haemophilia 10(Suppl 4):133–139CrossRefPubMed

Bolton-Maggs PH, Pasi KJ (2003) Haemophilias A and B. Lancet 361(9371):1801–1809CrossRefPubMed

Kolb-Kokocinski A, Mehrle A, Bechtel S et al (2006) The systemic functional characterization of Xq28 genes prioritises candidate disease genes. BMC Genomics 7:29CrossRefPubMedPubMedCentral

10.

Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D. GeneCards: encyclopedia for genes, proteins and diseases. Weizmann Institute of Science, Bioinformatics Unit and Genome Center (Rehovot, Israel), 1997. World Wide Web URL: http://www.genecards.org/

11.

Rosen N, Chalifa-Caspi V, Shmueli O, Adato A, Lapidot M, Stampnitzky J, Safran M, Lancet D (2003). GeneLoc: Exon-based integration of human genome maps. Bioinformatics 19(S1). URL: http://genecards.weizmann.ac.il/geneloc

12.

Nogueira A, Jorge P, Dores J et al (1993) X-linked adrenoleukodystrophy and haemophilia A in the same kindred. J Inherit Metab Dis 16(3):595–598CrossRefPubMed

13.

Guimaraes CP, Lemos M, Sa-Miranda C, Azevedo JE (2002) Molecular characterization of 21 X-ALD Portuguese families: identification of eight novel mutations in the ABCD1 gene. Mol Genet Metab 76(1):62–67 MayCrossRefPubMed

14.

Kondrashov AS (2003) Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Hum Mutat 21(1):12–27 JanCrossRefPubMed

15.

Lupski JR (2007) Genomic rearrangements and sporadic disease. Nat Genet 39(7 Suppl):S43–S47 JulCrossRefPubMed

Title: A family with combined mutations of the hemophilia A and X-linked adrenoleukodystrophy genes
Authors: Brent L. Fogel
Pari Young
Arthur R. Thompson
Susan Perlman
Publication date: 01-07-2008
Publisher: Springer Berlin Heidelberg
Published in: Neurogenetics / Issue 3/2008
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-008-0132-6

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A family with combined mutations of the hemophilia A and X-linked adrenoleukodystrophy genes

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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