C.A. Gregory

The gene for prolactin-inducible protein (PIP), uniquely expressed in exocrine organs, maps to chromosome 7

The hormonally responsive prolactin-inducible protein (PIP), gene is expressed in benign and malignant breast tumor tissues and in such normal exocrine organs as sweat, salivary, and lacrimal glands. In this communication we report the regional chromosome localization of the PIPgene locus to chromosome 7 by Southern hybridization to DNA from human-hamster somatic cell hybrids, and to 7q32–36 by in situ hybridization.

Somatic recombination rather than uniparental disomy suggested as another mechanism by which genetic imprinting may play a role in the etiology of Prader-Willi syndrome

SummarySix Prader-Willi syndrome (PWS) patients with normal karyotypes and their parents were analyzed to determine the nature of the molecular aberrations present in the proximal region of 15q and to determine the parental origin of the aberrant chromosome 15. In addition, the likehood that uniparental disomy plays a significant role in the etiology of PWS patients with normal karyotypes was studied. Restriction fragment length polymorphisms (RFLPs) recognized by seven probes [pML34 (D15S9), pTD3-21, pCGS0.9, pCGS1.1 (D15S10), IR4.3 (D15S11), IR10.1 (DS15S12), p189-1 (D15S13), IR39 (D15S18), and CMW-1 (D15S24)] mapping to the Prader-Willi chromosome region (PWCR) and an additional two probes [pMS1-14 (D15S1); the cDNA of neuromedin B] mapping elsewhere on chromosome 15 were analyzed in the six PWS patients and their parents. Copy number of each locus within the PWCR was determined by densitometry. Molecular rearrangements of the proximal region of 15q were observed in all of the six probands and the origin of the aberrant chromosome 15 when determined was consistently paternal in origin. While data obtained from our six patients does not support the mechanism of disomy, results obtained from three of the six patients show more complex rearrangements hypothesized to have resulted from somatic recombination. These rearrangements have resulted in acquired homozygosity and the lack of a paternal allele at various loci within the PWCR. The presence of only a maternal contribution at certain loci as the result of somatic recombination may be another mechanism by which genetic imprinting plays a role in the presentation of the PWS phenotype.

Characterization of cDNA Clones Corresponding to Genomic Loci Rearranged in Patients with Prader-Willi Syndrome

Genetic analysis of patients with Prader-Willi Syndrome (PWS) began with karyotyping of patients and their parents in the 1970 s and continued and expanded in the 1980’s with high resolution chromosome banding in an attempt to resolve the type of chromosome rearrangement. The results of high resolution banding in 280 patients with PWS has been summarized (Butler, 1990), and is a deletion of 15qll.2, q11-12, or q11–13 in 56%, a Robertsonian translocation in 0.7%, a reciprocal translocation in 0.7%, an extra isodicentric chromosome 15pter-qll in 1.4%, other chromosome abnormalities in 0.7%, and a normal karyotype in 41%. Furthermore, the aberrant chromosome 15 was found to be paternal in origin (Butler, 1990). These cytogenetic findings together with phenotype correlation studies showing no phenotypic differences between those PWS patients with or without a cytogenetic deletion, with the exception of hypopigmentation (Butler, 1989), led to the hypothesis that the patients without cytogenetically visible abnormalities may present as PWS as the result of a submicroscopic rearrangement within the region of 15q11–13.