Pure subtelomeric microduplications as a cause of mental retardation.

Submicroscopic subtelomeric aberrations are a common cause of mental retardation (MR). New molecular techniques allow the identification of subtelomeric microduplications, but their frequency and significance are largely unknown. We determined the frequency of subtelomeric, pure microduplications in a cohort of 624 patients with MR and/or multiple congenital anomalies using multiplex ligation dependent probe amplification (MLPA) and delineated the identified microduplications using array based comparative genomic hybridization (array CGH). In 11 patients, MLPA revealed a subtelomeric duplication without a concurrent deletion. Additional fluorescence in situ hybridization studies and parental analyses showed that three had occurred de novo: one duplication 5q34qter (12.7 Mb), one duplication 9q34.13qter (7.2 Mb) and one duplication 9p24.2pter (4.1 Mb). Five microduplications (9p, 11q, 12q, 15q and 16p) appeared to be inherited from an unaffected parent, while in three cases (9p, 12p and 17p) the parents were not available for testing. Based on our findings and data from the literature, the three de novo duplications were the only ones likely to be disease-causing, leading to a frequency of pathogenic subtelomeric, pure microduplications of 0.5%. Our study shows that subtelomeric microduplications are an infrequent cause of MR and that additional clinical and family studies are required to assess their clinical significance.

No justification of routine screening for 22q11 deletions in patients with overt cleft palate.

The velo-cardio-facial syndrome (VCFS), caused by a submicroscopic deletion of chromosome 22q11, is the most common syndrome that has palatal anomalies as a major feature. A possible strategy for early detection of VCFS is routine screening for 22q11 deletions in all infants with cleft palate (CP). The purpose of this study was to evaluate whether this strategy is preferable to testing on clinical suspicion. At the Nijmegen Cleft Palate Craniofacial Center, 58 new patients with overt CP were routinely tested, using fluorescence in situ hybridization (FISH), for a 22q11 deletion. One deletion was identified in a newborn girl with an overt CP who was clinically not suspected of having VCFS. Based on this study (n = 45) and the literature (n = 54), the prevalence of 22q11 deletions among children with CP, but without any other symptoms of VCFS, is estimated to be one in 99. We take the view that this figure is rather low and that early discovery will rarely have significant clinical or genetic consequences. Because CP patients remain under medical attention, almost all of the infants with isolated CP and VCFS will be recognized as having the syndrome at a later age when additional features have developed. Therefore, we conclude that routine FISH testing for 22q11 deletions in infants with overt CP is not indicated, provided clinical follow-up is guaranteed.

Short term fasting does not aggravate immunosuppression in harbour seals (Phoca vitulina) with high body burdens of organochlorines.

Two groups of 11 harbour seals (Phoca vitulina) with different body burdens of organochlorines were subjected to an experimental 15-day fasting period, during which they lost an average 16.5% of their body weights. Blood levels of the most persistent organochlorines showed an approximate twofold increase, while levels of aryl hydrocarbon receptor-binding organochlorines remained largely unaffected. Few differences in immunological parameters were observed between the two dietary groups. Numbers of circulating lymphocytes dropped to about 65% of the initial values and NK cell activity showed a slight increase in both groups. Mitogen- and antigen-induced lymphoproliferative responses of the Baltic group of seals remained within normal ranges. These results suggest that relatively short-term fasting periods do not present an additional immunotoxicological risk to seals with high body burdens of organochlorines.