Uniparental disomy (UPD) for fra(X) in a 47,XXY male

We report a 4-year-old hyperactive, mentally retarded male with 47,XXY and UPD for fra(X). Speech and motor delay were first noted at age 15 months. He has no dysmorphic features, normal ears, hyperextensible joints, small testes, and no history of seizures. His mother has prominent lowest ears, a long midface, anteverted nostrils, hyperextensible joints, malocclusion, and had learning problems in school. Routine chromosome analysis revealed the proband to be 47,XXY. Parental chromosomes were normal in number. The proband was fra(X) positive [30/160 cells, 18%]. No cells had two expressed fra(X)s; however, this may be a function of the low level of expression and the number of cells scored. Maternal cells were also fra(X) positive [19/205, 9.2%]. Southern analysis demonstrated the mother to be heterozygous for a methylated, full mutation (>220 repeats); her normal FMR-1 gene was disproportionately unmethylated. The proband had two fully expanded and methylated FMR-1 genes, one the same size as the maternal gene and the other >620 repeats. RFLP analysis revealed a maternal meiotic II error, the result of which was UPD of the X chromosome.