Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker

Cytogenetic analysis in a girl with multiple congenital anomalies indicatin g Pallister-Killian syndrome (PKS) showed a supernumerary marker chromosome in 1/76 lymphocytes and 34/75 fibroblast metaphases. GTG-banding pattern w as consistent with the chromosomal region 12pter-12q11. While fluorescence- in-situ hybridisation (FISH) with a whole chromosome 12 painting probe conf irmed the origin of the marker, a chromosome 12 specific alpha -satellite p robe did not hybridise to it. FISH analysis with a specific subtelomeric pr obe 12p showed hybridisation to both ends of the marker chromosome. High-re solution multicolour-banding (MCB) studies revealed the marker to be a der( 12)(pter --> p12.3::p12.3 --> pter). Summarlsing the FISH information, we d efined the marker as an inverted duplication of 12pter-12p12.3 leading to p artial tetrasomy of chromosome 12p. In skin fibroblasts, cultured at the pa tient's age of 1 year and 9 years, the marker chromosome was found in simil ar frequencies, even after several culture passages. Therefore, we consider the marker to have a functional centromere although it lacks detectable ce ntromeric alpha -satellite sequences. To the best of our knowledge, this is the first proven analphoid marker of chromosome 12. Molecular genetic stud ies indicated that this marker is of paternal origin. The finding of partia l tetrasomy 12pter-12p12.3 in our PKS patient allows to narrow down the cri tical region for PKS.