title: Mosaic loss of 15q11q13 in a patient with hypomelanosis of Ito: is there a role for the P gene?
abstract: We report a patient with mental retardation, behavioral disturbances, and pigmentary anomalies, consistent with the phenotype of hypomelanosis of Ito (HMI), and in whom cytogenetic analysis revealed mosaicism for an unbalanced translocation. His karyotype is 45, XY,-7,-15,+der(7)(7:15)t(q34:q13)/46,XY. He is therefore monosomic for 7q34 to qter and 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 associated with abnormalities of pigmentation, such as the hypopigmentation seen in patients with deletions of 15q11q13, and the Prader-Willi and Angelman syndromes. Mutations within the P gene have also been associated with tyrosinase-positive (type II) oculocutaneous albinism. Using fluorescence in situ hybridization, we confirmed that our patient is deleted 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 heterogeneous disorder, we postulate that, in our case and potentially in others, this phenotype may result directly from the loss of specific pigmentation genes.
authors.affiliation: Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Pellegrino
authors.forename: R E
authors.initials: RE
authors.lastname: Schnur
authors.forename: R
authors.initials: R
authors.lastname: Kline
authors.forename: E H
authors.initials: EH
authors.lastname: Zackai
authors.forename: N B
authors.initials: NB
authors.lastname: Spinner
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009030:Mosaicism; D010859:Pigmentation Disorders / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human