Context-Chromosomalabnormalities that involve the proximal region of chromosome 15q occur relatively frequently in the human population. However, interstitial triplications involving one 15 homologue are very rare with three cases reported to date. Objective-To provide a detailed molecular characterisation of four additional patients with interstitial triplications of chromosome 15q11-q14. Design-Molecular analyses were performed using DNA markers and probes specific for the 15q11-q14 region. Setting-Molecular cytogenetics laboratory at the University of Chicago. (15)). In all patients the orientation of the triplicated segments was normalinverted-normal, suggesting that a common mechanism of rearrangement may have been involved. Microsatellite analysis showed the parental origin of the trip(15) to be maternal in three cases and paternal in one case. The paternal triplication patient had features similar to PWS, one maternal triplication patient had features similar to AS, and the other two maternal triplication patients had non-specific findings including hypotonia and mental retardation. Methylation analysis at exon 1 of the SNRPN locus showed increased dosage of either the paternal or maternal bands in the paternal or maternal triplication patients, respectively, suggesting that the methylation pattern shows a dose dependent increase that correlates with the parental origin of the triplication. In addition, the expression of SNRPN was analysed by northern blotting and expression levels were consistent with dosage and parental origin of the triplication. Conclusions-These four additional cases of trip(15) will provide additional information towards understanding the phenotypic eVects of this abnormality and aid in understanding the mechanism of formation of other chromosome 15 rearrangements. (J Med Genet 2001;38:26-34)

We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 15q with evidence of a terminal deletion of the same rearranged chromosome. The proband was a multiple congenital malformed female with a prenatal diagnosis of trisomy 15q and an extremely severe clinical course. The phenotype of the patient was characterized by marked intrauterine growth retardation, congenital heart defect, "horseshoe" kidney, hand contractures, and clubfeet. The exitus came at 20 days because of progressive cardio-respiratory impairment. Overall, the clinical phenotype appeared more severe than usual trisomy 15q syndrome. Postnatal cytogenetic and molecular studies unraveled a "de novo" inverted duplication of 15q (q21.3-->q26.3), associated with the deletion of the 15q telomere and part of the band 15q26.3. A single copy region spanning approximately 600 kb between the duplicated segments was present. Correlation between the clinical findings of the patient and the phenotype of trisomy 15q reported in literature is also provided.

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