title: Male-to-male transmission of X-linked Alport syndrome in a boy with a 47,XXY karyotype.
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.
authors.affiliation: Laboratori de Biologia Molecular, Fundació Puigvert, Universitat Autònoma Barcelona, Barcelona, Spain. ears@fundacio-puigvert.es
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ars
authors.forename: Bárbara
authors.initials: B
authors.lastname: Tazón-Vega
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz
authors.forename: Carme
authors.initials: C
authors.lastname: Nogués
authors.forename: Núria
authors.initials: N
authors.lastname: Arnedo
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Rajmil
authors.forename: Roser
authors.initials: R
authors.lastname: Torra
mesh_terms: D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y; D020732:Cytogenetic Analysis / Q000379:methods; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D040181:Genetic Diseases, X-Linked; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D007713:Klinefelter Syndrome / Q000150:complications / Q000235:genetics*; D008297:Male; D009394:Nephritis, Hereditary / Q000150:complications / Q000235:genetics*; D010641:Phenotype