SUPERNUMERARY INV DUP(15) IN A PATIENT WITH ANGELMAN SYNDROME AND A DELETION OF 15Q11-]13

We have studied a patient with Angelman syndrome (AS) and a 47,XY,+inv dup(15) (pter-->q11::q11-->pter) karyotype, Molecular cytogenetic stu dies demonstrated that one of the apparently normal 15s was deleted at loci D15S9, GABRB3, and D15S12, There were no additional copies of th ese loci on the inv dup(15). The inv dup(15) contained only the perice ntromeric sequence D15Z1. Quantitative DNA analysis confirmed these fi ndings and documented a standard large deletion of sequences from 15q1 1-q13, as usually seen in patients with AS, DNA methylation testing at D15S63 showed a deletion of the maternally derived chromosome. AS in this patient can be explained by the absence of DNA sequences from chr omosome 15q11-q13 on one of the apparently cytogenetically normal 15s, and not by the presence of an inv dup(15), This is the fourth patient with an inv dup(15) and AS or Prader Willi syndrome, who has been stu died at the molecular level. In ah cases an additional alteration of c hromosome 15 was identified, which was hypothesized to be the cause of the disease. Patients with inv dup(15)s may be at increased risk for other chromosome abnormalities involving 15q11-q13. (C) 1995 Wiley-Lis s, Inc.