Abstract
Alport syndrome (AS) is a genetically heterogeneous renal hereditary disease. Male-to-male transmission has been considered fully indicative of autosomal dominant AS. We report a family with male-to-male transmission of X-linked AS due to an extra X chromosome of paternal origin in the proband. Linkage analysis excluded the autosomal loci and demonstrated segregation with the COL4A5 locus (Xq22.3). Sperm FISH analysis from his father detected an increased XY disomy. Mutation screening of the COL4A5 gene identified a splicing mutation, c.4688G>A. The proband and his paternal grandmother showed random X chromosome inactivation. However, a preferential expression of the aberrantly spliced transcript was detected in the proband when compared to his grandmother. This finding could explain why the AS phenotype of this 47,XXY boy resembles more an affected male than a female carrier. This is the first reported case of concurrence of Alport and Klinefelter syndromes.
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Acknowledgements
We thank the family for taking part in this study. We also thank Dr Moisès Burset and Helena Kruyer for correction of the manuscript. This work was supported by grants of the Ministerio de Sanidad (02/3672, Infraestructura 2002), the Red de Enfermedades Metabólicas Hereditarias (03/054), the Ministerio de Ciencia y Tecnología (BFI2002-01193) and the Generalitat de Catalunya (2001SGR-00202), Spain.
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Ars, E., Tazón-Vega, B., Ruiz, P. et al. Male-to-male transmission of X-linked Alport syndrome in a boy with a 47,XXY karyotype. Eur J Hum Genet 13, 1040–1046 (2005). https://doi.org/10.1038/sj.ejhg.5201452
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DOI: https://doi.org/10.1038/sj.ejhg.5201452
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