Male-to-male transmission of X-linked Alport syndrome in a boy with a 47,XXY karyotype.
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.
Ars
Elisabet
E
Laboratori de Biologia Molecular, Fundació Puigvert, Universitat Autònoma Barcelona, Barcelona, Spain. ears@fundacio-puigvert.es
Tazón-Vega
Bárbara
B
Ruiz
Patricia
P
Nogués
Carme
C
Arnedo
Núria
N
Rajmil
Osvaldo
O
Torra
Roser
R
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