Male-to-male transmission of X-linked Alport syndrome in a boy with a 47,XXY karyotype

Elisabet Ars, Barbara Tazón-Vega, Patricia Ruiz, Carme Nogués, Núria Arnedo, Osvaldo Rajmil, Roser Torra

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)


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. © 2005 Nature Publishing Group All rights reserved.
Original languageEnglish
Pages (from-to)1040-1046
JournalEuropean Journal of Human Genetics
Publication statusPublished - 1 Dec 2005


  • Alport syndrome
  • COL4A5 splicing mutation
  • Klinefelter syndrome
  • Linkage analysis
  • Male-to-male transmission
  • Sperm aneuploidy
  • X chromosome inactivation


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