Prenatal diagnosis of a mosaic supernumerary marker iso (8p) (tetrasomy 8p): discordance between chorionic villi culture and amniotic fluid karyotypes

We describe the first case of mosaic supernumerary marker iso (8p) displaying a karyotype discordance between chorionic villi (CV) and amniotic fluid (AF) cultures during prenatal cytogenetic diagnosis. In the first trimester, cytogenetic analysis after chorionic villi sampling (CVS) was normal in all metaphases in the short-term cytotrophoblast cell culture, but an undefined supernumerary marker was detected in 60% of mesenchymal cells in the long-term CV culture. Informed of the mosaicism, the couple selected amniotic fluid sampling as a second-trimester confirmatory diagnostic procedure. The supernumerary marker was absent in all of the 25 available AF cells metaphases. The prospective parents received genetic counselling and were informed that the discordance could be interpreted as a placental confined mosaicism or as a true foetal mosaicism with low percentage of affected cells. The couple opted to continue the pregnancy. In the second month of life, the child had abnormal development with severe psychomotor delay and frequent episodes of epilepsy. Postnatal cytogenetic extensive re-evaluation discovered that the previously detected supernumerary marker was indeed an isochromosome (8p) rearrangement present at low frequency in 5% of the blood lymphocytes. Copyright (C) 2006 John Wiley & Sons, Ltd

Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic population isolate of Sardinia

Thiopurine S-methyltransferase (TPMT) is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it was shown that inter-individual differences in response to these drugs is largely determined by genetic variation at the TPMT locThiopurine S-methyltransferase (TPMT) is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it was shown that inter-individual differences in response to these drugs is largely determined by genetic variation at the TPMT locu

Detection of a BAC clone duplication in 17p11.2 in two unrelated patients, affected by severe epileptic encephalopathy, by genome array CGH: a new variant of Potochy-Lupsky syndrome?

The duplication 17p11.2 syndrome, associated with dup(17)(p11.2p11.2), is a recently recognized syndrome of multiple congenital anomalies and mental retardation. It was the first described reciprocal micro-duplication syndrome that was predicted to be a reciprocal of a micro-deletion syndrome. It is the reciprocal of the Smith–Magenis syndrome caused by a micro-deletion of the same segment on 17p (Potocky et al. 2007). We report a novel pathological variant of this syndrome, detected by genome array-CGH, in two unrelated subjects with dup(17)(p11.2p11.2), The array analysis was performed using the BAC Cyto-chips Blue-Gnome platform, at 0.5-Mb median resolution, and revealed the presence of the same BAC duplication in both patients. Fluorescence in situ hybridization analysis with the same BAC did not resolve the duplication. The duplicated BAC (RP11-78O7), of about 140 K, maps in 17p11.2 and contains an interesting gene, presumably involved in the pathology. The parents did not show the duplication, suggesting that it was a de novo rearrangement. Cytogenetic and clinical features of subjects with partial trisomy of proximal 17p have been described, mostly in isolated case reports or literature reviews. These nonspecific and non-characteristic findings include developmental delay, mental retardation and dysmorphic features. Our patients present a particular form of epileptic encephalopathy associated with severe mental retardation and autistic behaviour. Molecular and genetic studies are in progress to define and characterize the rearrangement and for better genotype/phenotype correlatio