De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch.

Prader-Willi syndrome (PWS) is a neurogenetic disease characterized by infantile hypotonia, gonadal hypoplasia, obsessive behaviour and neonatal feeding difficulties followed by hyperphagia, leading to profound obesity. PWS is due to a lack of paternal genetic information at 15q11-q13 (ref. 2). Five imprinted, paternally expressed genes map to the PWS region, MKRN3 (ref. 3), NDN (ref. 4), NDNL1 (ref. 5), SNRPN (refs 6-8 ) and IPW (ref. 9), as well as two poorly characterized framents designated PAR-1 and PAR-5 (ref. 10). Imprinting of this region involves a bipartite 'imprinting centre' (IC), which overlaps SNRPN (refs 10,11). Deletion of the SNRPN promoter/exon 1 region (the PWS IC element) appears to impair the establishment of the paternal imprint in the male germ line and leads to PWS. Here we report a PWS family in which the father is mosaic for an IC deletion on his paternal chromosome. The deletion chromosome has acquired a maternal methylation imprint in his somatic cells. We have made identical findings in chimaeric mice generated from two independent embryonic stem (ES) cell lines harbouring a similar deletion. Our studies demonstrate that the PWS IC element is not only required for the establishment of the paternal imprint, but also for its postzygotic maintenance.

Epidermal growth factor receptor and estrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal patients.

AIMS AND BACKGROUND: The purpose of our research was to investigate the relations between the levels of epidermal growth factor receptor and estrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal Polish women. METHODS: Cell membrane levels of epidermal growth factor receptor (EGF-R), and cytosol (c) estrogen (ER) and progesterone (PR) receptors were determined in 221 specimens of primary breast cancers. ERc and PRc were assayed using the dextran-coated charcoal procedure, and EGF-R were assayed by the radioligand method of specific saturation of the crude membrane fraction with 125I-EGF RESULTS: A statistically significant inverse correlation was found in all tumors between the concentrations of EGF-R and ERc, whereas for PRc significance of this correlation was not fully confirmed. ERc concentrations in tumors were positively correlated with age of patients, whereas EGF-R and PRc were not. In all, in premenopausal, and in postmenopausal EGF-R-positive tumors (> or = 10 fmol/mg of membrane protein), mean concentrations of ERc did not differ significantly. These groups of tumors seem to be homogeneous with respect to ERc concentrations. In EGF-R-negative (< 10 fmol/mg of membrane protein) postmenopausal tumors, the mean ERc concentration was significantly higher than in premenopausal tumors, hence these groups of tumors appear to be heterogeneous with regard to ERc contents: CONCLUSIONS: The present findings may have significance in differentiation of postmenopausal breast cancer.

[Early detection and differentiation of congenital heart diseases (author's transl)]. / Wczesne wykrywanie i róznicowanie wad wrodzonych serca

Observations have been carried out on 116 neonates and infants with congenital heart malformations, and cardiomyopathies; 75 of them died. The initial diagnosis was made at Maternity Hospitals or at Infants' Wards, mainly in county hospitals of the province of Gdansk. Afterwards these children were sent to the pediatric cardiology ward of the Pediatric Institute in Gdansk, where the diagnoses were verified. Catheterisation and angiocardiography were performed in 29 children; 18 patients were treated surgically due to operable heart malformations. Rashkind's balloon atrioseptostomy was performed in three infants. The diagnosis based on physical ECG and X-rays was correct in only 42% of cases, and was most accurate in children with transposition of the great arteries, syndrome of Fallot, coarctation of the aorta and ventricular septal defects. The greatest difficulties were caused by the cases with hypoplastic left heart syndrome, double outlet of the right ventricle, single ventricle. They suggested that the initial clinical diagnosis should be confirmed by hemodynamic data and angiocardiography.

[The analysis of complications and mortality rate of children with congenital heart diseases (author's transl)]. / Analiza przyczyn powiklan i smiertelnosci u dzieci z wadami wrodzonymi serca

The highest mortality rate among 75 newborns and infants observed has been noted in children with hypoplastic left heart syndrome, transposition of the great arteries, double outlet of the right ventricle and single ventricle. In the newborn period the mortality rate was 96%, and later on it decreased. Cardiac failure complicated by pneumonia was the most frequent cause of the infant's death (47 cases), then anoxic spells and sudden death (12 cases), diagnostic and surgical procedures (10 cases). The causes of death of six children were apparently not related to the heart disease.

[Myocardial infarction in children]. / Zawal serca u dzieci.

Twenty nine patients with myocardial infarction (MI) of different etiology were analysed. The diagnosis was based on routine clinical examination with ECG predominance. In certain cases cardiac catheterisation with cineangiography and scintigraphy were performed. Myocardial infarction the most often was observed in Bland-White-Garland syndrome (15 cases). In 5 cases MI was found in heart muscle disease, in 3 cases in critical aortic stenosis, and in singular cases in progeria syndrome, bacterial endocarditis and after surgical procedure. In 2 older children the etiology of MI was difficult to establish. Clinical picture of MI in children is different in comparison with adult person. Chest pain, typical for MI in adults, is difficult to diagnose particularly in infants. Localisation of MI is also different, predominant is anteroseptal, lateral, subendocardial and papillary muscle infarction. Relative small number of MI in children is due to difficulty in interpretation of clinical picture and to low popularity of ECG examination in this group of age.

Atrioventricular septal defect: clinical and diagnostic problems in children hospitalised in 1993-1998.

INTRODUCTION: Atrioventricular septal defect (AVSD) is one of the most frequent congenital heart diseases, making up 7.5% of all developmental anomalies of circulatory system. MATERIAL AND METHODS: Sixty-seven children with the diagnosis of atrioventricular septal defect were hospitalised at the Department of Paediatric Cardiology, Medical University in Gdansk, in 1993-1998. Patients' age ranged at diagnosis between 3 days and 17 years (mean age 35 months). The analysed group included 20 children with partial atrioventricular septal defect (group I) and 47 children with complete AVSD (group II). The diagnosis was based on anamnesis, physical examination, ECG, chest x-ray and echocardiography. Cardiac catheterisation and angiocardiography were performed in 28 children. RESULTS: On the basis of the results obtained, 6 children with Down syndrome were disqualified from the surgery due to persistent pulmonary hypertension. Fifty-nine children--including all the patients from group I (20) and 39 children from group II were qualified for operations in extracorporeal circulation. Two children from group II required ventilation with the mixture containing NO in the early post-operative period. There were 8 deaths (12%). Three children from group II died preoperatively due to severe generalised infection in early infancy and 5 infants from group II died immediately after operation. No deaths occurred in group I. In one case of a 4 year-old boy with partial atrioventricular septal defect, atrioventricular block developed immediately after surgery and required constant stimulation of the heart. In two children it was necessary to replace mitral valve (2 and 5 years after ASD I surgery). CONCLUSIONS: 1. Children with Down syndrome require screening echocardiography. 2. Non-invasive diagnostic examinations of atrioventricular septal defect are usually sufficient for the full assessment of the defect and the choice of further treatment. 3. The correction of the congenital heart disease such as atrioventricular septal defect should be completed in the first 6 months of life, particularly in children with complete AVSD.

A case of Prader-Willi syndrome arising as a result of familial unbalanced translocation t(11;15)(q25;q13).

We report on a case of Prader-Willi syndrome (PWS) with a true reciprocal unbalanced translocation, 45,XX,-15,der(11)t(11;15)pat. The proposita was diagnosed clinically as having severe PWS. Molecular studies revealed loss of the paternal methylation pattern at locus D15S63 and a deletion encompassing the loci from at least D15S10 to D15S97 of paternal chromosome 15. FISH studies confirmed the deletion of 15q11q13 region and the presence of two telomeres on all chromosomes. The proposita's father, the father's sister and their mother are all carriers of the same balanced translocation t(11;15)(q25;q13). By genomic imprinting we would expect that if the father's sister were to give birth to a child with the same unbalanced translocation as the proband, it would be affected by Angelman syndrome. To date, a similar familial unbalanced translocation due to loss of the small chromosome15 derivative has not been described.