Unbalanced translocation t(15;22) in 'severe' Prader-Willi syndrome

A 13-year-old girl with an unbalanced karyotype 45,XX,-15,der(22)t(15;22)(q 13;q13.3) de novo had Prader-Willi syndrome (PWS), (score 13.5), but with f eatures of mental and physical retardation more severe than usually seen in PWS. The clinical diagnosis of PWS was confirmed by methylation analysis t hat showed absence of the paternal band. With GTG banding, the cytogenetic breakpoint on chromosome 15q13, with 15q14 intact, encompassed the PWS regi on, while the breakpoint on 22q was terminal. Investigations with FISH util ised ten different probes/combinations, namely SNRPN/PML, TUPLEI/22q13.3, T UPLE/ARSA, GABRB3, three YAC clones and one cosmid for specific regions wit hin chromosome 15q, painting probes for the long arm of chromosomes 15 and 22 and a pantelomere probe. Deletion of SNRPN,TYAC 9 (at 15q11-12), TYAC19 (at 15q13) and GABRB3 (within the PWS locus), was evident on the derivative (22) chromosome, while TYAC10 (at 15q22), cos15 (at 15q22) and PML (15q22) were not deleted. On the der(22), 22q13.3 and ARSA were not deleted, but t he most distal non specific pantelomeric probe was deleted. Thus, the sever e phenotype could be attributable to deletion on chromosome 15q extending b eyond q13 to q14, (further than the usual chromosome 15q deletion (q11-13) in PWS), or be related to loss of the very terminal 22q region (from ARSA t o the pantelomere) or be due to genetic factors elsewhere in the genome. (C ) 2000 Editions scientifiques et medicales Elsevier SAS.