Mouse mutants carrying deletions that remove the genes mutated in Coffin-Lowry syndrome and lactic acidosis

The mouse X-linked mutants lined and stripey are associated with lethality of affected males in utero and a striping of the coat in carrier females. We demonstrate that the underlying mutations are nested deletions which lie in the Phex-Amelx chromosomal segment conserved between man and mouse. The lined deletion contains less than approximately 0.7 cM of genetic material and includes the growth factor- regulated protein kinase gene, Rsk2. Stripey carries a larger deletion which removes approximately 2.0 cM of genetic material, including Rsk2 and the pyruvate dehydrogenase E1alpha subunit gene, Pdha1 . Since Coffin-Lowry syndrome and neonatal lactic acidosis are associated with mutations in the human homologues of Rsk2 and Pdha1 respectively, lined and stripey provide models for gene deficiencies in these disorders.      

Complications affecting preterm neonates from 1991 to 2006: what have we gained?

Aim: In this study, we determined whether outcome of preterm neonates has improved over a period of 16 years. Study design: Inborn neonates with a gestational age of 25.0–29.9 weeks were included. Patients with severe congenital malformations were excluded. Mortality and morbidity (chronic lung disease; CLD, intraventricular haemorrhage: IVH grade III or IV, cystic periventricular leukomalacia: cPVL, perforated necrotizing enterocolitis: NEC, severe retinopathy of prematurity needing surgery: ROP and cerebral palsy: CP) were compared in three periods (period 1: 1991–1996 n = 434; period 2: 1997–2001 n = 356; period 3: 2002–2006 n = 422). Results: Infant mortality decreased from 15.2% to 10.9%. CLD did not differ significantly between periods (14.1–14.8%). Perforated NEC decreased from 2.8% to 1.6%. IVH grade III and IV both remained at 5.7% in period 3, whereas cPVL decreased significantly from 4.5% to 1.6%. Cerebral palsy decreased from 5.8% to 3.5% in period 3. Two neonates in each period were in need of surgery for ROP. Conclusion: Inborn preterm patients showed an improved survival and a significant reduction in cPVL and CP. Perforated NEC showed a trend to decrease. CLD and IVH grade III and IV remain a matter of concern.     

Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles

Canals I, Elalaoui SC, Pineda M, Delgadillo V, Szlago M, Jaouad IC, Sefiani A, Chabás A, Coll MJ, Grinberg D, Vilageliu L. Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles. The Sanfilippo syndrome type C [mucopolysaccharidosis IIIC (MPS IIIC)] is caused by mutations in the HGSNAT gene, encoding an enzyme involved in heparan sulphate degradation. We report the first molecular study on several Spanish Sanfilippo syndrome type C patients. Seven Spanish patients, one Argentinean and three Moroccan patients were analysed. All mutant alleles were identified and comprised nine distinct mutant alleles, seven of which were novel, including four missense mutations (p.A54V, p.L113P, p.G424V and p.L445P) and three splicing mutations due to two point mutations (c.633+1G>A and c.1378‐1G>A) and an intronic deletion (c.821‐31_821‐13del). Furthermore, we found a new single nucleotide polymorphism (SNP) (c.564‐98T>C). The two most frequent changes were the previously described c.372‐2A>G and c.234+1G>A mutations. All five splicing mutations were experimentally confirmed by studies at the RNA level, and a minigene experiment was carried out in one case for which no fibroblasts were available. Expression assays allowed us to show the pathogenic effect of the four novel missense mutations and to confirm that the already known c.710C>A (p.P237Q) is a non‐pathogenic SNP. Haplotype analyses suggested that the two mutations (c.234+1G>A and c.372‐2A>G) that were present in more than one patient have a common origin, including one (c.234+1G>A) that was found in Spanish and Moroccan patients.     

Graduates of different UK medical schools show substantial differences in performance on MRCP(UK) Part 1, Part 2 and PACES examinations

Background  

The UK General Medical Council has emphasized the lack of evidence on whether graduates from different UK medical schools perform differently in their clinical careers. Here we assess the performance of UK graduates who have taken MRCP(UK) Part 1 and Part 2, which are multiple-choice assessments, and PACES, an assessment using real and simulated patients of clinical examination skills and communication skills, and we explore the reasons for the differences between medical schools.     

Paediatric acute peritoneal dialysis in southern Nigeria

Background

Acute peritoneal dialysis (APD) is the preferred treatment for isolated failure of the kidney. The authors reviewed children with acute renal failure (ARF) who had APD in Port Harcourt, Nigeria.

Results

221 patients, 147 boys and 74 girls (M: F, 1.99:1), mean (SD) age 5.4 (4.9) years had ARF. Dialysis was indicated in 112 cases. The main clinical indication being convulsion/uraemia 30 (26.8%) Only 27 patients (21 boys and 6 girls) had APD, giving an access rate of 24.1%. The commonest dialysis related complication was catheter malfunction 12 (44.4%). The mortality rate among the dialysed patients was 22.2%. Lack of dialysis and intractable hypertension significantly increased mortality (χ² = 7.13, p<0.01) and (χ² = 14.9, p<0.001) respectively.

Conclusion

APD is effective in reducing mortality of children with ARF. However, there were low dialysis access rate and few complications.