MOSAIC LOSS OF 15Q11Q13 IN A PATIENT WITH HYPOMELANOSIS OF ITO - IS THERE A ROLE FOR THE P-GENE

We report a patient with mental retardation, behavioral disturbances, and pigmentary anomalies, consistent with the phenotype of hypomelanos is of Ito (HMI), and in whom cytogenetic analysis revealed mosaicism f or an unbalanced translocation. His karyotype is 45, XY,-7, -15,+der(7 )(7;15)t(g34;q13)/46, XY. He is therefore monosomic for 7q34 to qter a nd 15pter to q13 in the cells containing the translocation. The human homolog (P) of the p gene (the product of the mouse pink-eyed dilution locus) maps to 15q11q13. Loss of this locus is believed to be associa ted with abnormalities of pigmentation, such as the hypopigmentation s een in patients with deletions of 15q11q13, and the Prader-Willi and A ngelman syndromes. Mutations within the P gene have also been associat ed with tyrosinase-positive (type II) oculocutaneous albinism. Using f luorescence in situ hybridization, we confirmed that our patient is de leted for one copy of a P gene probe in the cells with the unbalanced translocation, and for loci within the region critical for the Prader- Willi/Angelman syndromes. Although hypomelanosis of Ito is a heterogen eous disorder, we postulate that, in our case and potentially in other s, this phenotype may result directly from the loss of specific pigmen tation genes.