MATERNAL UNIPARENTAL ISODISOMY OF HUMAN-CHROMOSOME-14 ASSOCIATED WITHA PATERNAL T(13Q14Q) AND PRECOCIOUS PUBERTY

Cytogenetic and molecular investigation of a boy with precocious puber ty and motor developmental delay revealed a 45,XY,t(14q14q) or i(14q) karyotype with no paternal chromosome 14 contribution. VNTR analysis o f loci on four other chromosomes excluded non-paternity with greater t han 99% confidence. Results of VNTR and CA repeat analyses of ten loci along the entire length of chromosome 14 were consistent with homozyg osity at all loci, suggesting that the chromosomal rearrangement was a maternal isochromosome for 14q. As the proband's father had a balance d Robertsonian translocation, t(13q14q), we suggest that the origin of the maternal uniparental disomy (UPD) was fertilization by a nullisom y 14 sperm with formation of the isochromosome in the early embryo. Al so, the proband has several clinical features in common with six previ ously reported liveborn cases of maternal UPD 14: hypotonia and motor developmental delay, mild dysmorphic facial features, low birth weight and growth abnormalities, and, more specifically, precocious puberty among the four cases old enough to assess. The emergence of a syndrome associated with maternal UPD 14 suggests the possibility of genomic i mprinting of regions of chromosome 14, especially a gene involved in t he onset of puberty.