title: XX sex reversal, palmoplantar keratoderma, and predisposition to squamous cell carcinoma: genetic analysis in one family.
abstract: We describe a large inbred Sicilian family that includes four 46, XX (SRY-) brothers. Palmoplantar hyperkeratosis (PPK) and an associated predisposition to squamous cell carcinoma (SCC) of the skin, segregates as a recessive trait within the family. Interestingly, all the PPK-affected members of the family are phenotypic males (46,XY or 46,XX) while seven XX sibs are healthy phenotypic females with no signs of PPK. We propose that homozygosity for a single mutational event, possibly including contiguous genes, may cause PPK/SCC in both XY or XX individuals and sex reversal in XX individuals. The family is informative for linkage analysis for the PPK trait and allows linkage exclusion for the sex reversal trait. Here we show that 15 loci involved in PPK etiology, skin differentiation, function or malignancy, and nine loci involved in sex determination/differentiation are not implicated in the phenotype of this family.
authors.affiliation: Dipartimento di Patologia Umana ed Ereditaria, Sezione di Biologia Generale e Genetica Medica, Università di Pavia, Pavia, Italia.
authors.forename: Orietta
authors.initials: O
authors.lastname: Radi
authors.forename: Pietro
authors.initials: P
authors.lastname: Parma
authors.forename: Sandrine
authors.initials: S
authors.lastname: Imbeaud
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Nasca
authors.forename: Filippo
authors.initials: F
authors.lastname: Uccellatore
authors.forename: Paola
authors.initials: P
authors.lastname: Maraschio
authors.forename: Luciano
authors.initials: L
authors.lastname: Tiepolo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Micali
authors.forename: Giovanna
authors.initials: G
authors.lastname: Camerino
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008126:Lod Score; D008297:Male; D010375:Pedigree; D019849:Sex Determination Processes; D012878:Skin Neoplasms / Q000235:genetics*