Homozygosity mapping of a third Joubert syndrome locus to 6q23.

BACKGROUND: Joubert syndrome (JS) is a recessively inherited disorder characterised by hypotonia at birth and developmental delay, followed by truncal ataxia and cognitive impairment, characteristic neuroimaging findings (cerebellar vermis hypoplasia, "molar tooth sign") and suggestive facial features. JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys. JS is also genetically heterogeneous, with two known loci, on 9q34 (JBTS1) and 11p11-q12 (CORS2), representing only a fraction of cases. METHODS: A large consanguineous Joubert family (five affected) was analysed for linkage with a marker set covering the entire genome and 16 smaller families were subsequently tested for candidate loci. RESULTS: We report here the identification of a third locus in 6q23 (JBTS3) from the study of two consanguineous families. LOD score calculation, including the consanguinity loops, gave a maximum value of 4.1 and 2.3 at q = 0 for the two families, respectively. CONCLUSIONS: Linkage between the disease and the D6S1620-D6S1699 haplotype spanning a 13.1 cM interval is demonstrated. Genotype-phenotype studies indicate that, unlike CORS2, JBTS3 appears not to be associated with renal dysfunction.

Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother's milk during anaemia of prematurity.

Twenty-four premature infants, < 32 weeks gestational age, were randomly assigned in a double-blind, placebo-controlled trial to 6 weeks of treatment with either recombinant human erythropoietin (rHuEpo) 150 U/kg three times per week given sc (n = 12) or placebo (n = 12). The infants were fed a diet rich in protein (3.2 g/kg/day) and energy (130 kcal/kg/day) based on their own mother's milk fortified with bovine protein together with moderate iron supplementation (4 mg/kg/day). During the treatment (rHuEpo versus placebo) significant differences in mean (+/- SD) reticulocyte count (4.8 +/- 1.2 versus 2.7 +/- 1.4%; p < 0.01), mean packed red cell volume (PCV) (0.38 +/- 0.03 versus 0.34 +/- 0.04, p < 0.05) and mean haemoglobin concentration (12.6 +/- 1.1 versus 11.5 +/- 1.2 g/100 ml; p < 0.05) were found. Within the rHuEpo group, PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group. No indications of iron deficiency were seen. We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity. High iron supplementation does not seem to be essential for a significant erythropoietic response. No adverse effect attributable to rHuEpo was observed.

Ehlers-Danlos syndrome and diverticula of the bladder.

Cases of two boys, 6 and 4 years old respectively, with Ehlers-Danlos syndrome (EDS) and large bladder diverticula, are reported. Diverticulectomies were performed, but large diverticula reappeared in both patients. A connection between the increased extensibility of the connective tissue in EDS and the development of bladder diverticula is suggested.

Rapid diagnosis of respiratory syncytial virus and influenza A virus infections by immunofluorescence: experience with a simplified procedure for the preparation of cell smears from nasopharyngeal secretions.

A simplified procedure for preparing direct smears of exfoliated cells from nasopharyngeal secretions is presented. The specimens were examined by the indirect immunofluorescence (IF) technique for the presence of respiratory syncytial (RS) virus and influenza A virus antigens. Specimens from 457 children hospitalised at twelve different hospital departments in Norway were examined during the winter season 1980-81. RS virus was identified in samples from 139 children and influenza A virus from 28. Results of IF examinations for RS virus were copositive with serology in 19 of 23 cases (83%) and with probably no false positive results. Samples from 29 children were also prepared by the conventional washing technique. RS virus was identified in 18 of these specimens. Seventeen of these were also found positive by the simplified method. This comparison was done blind. Compared to results of virus isolation and serology the IF examinations for influenza A virus were somewhat less sensitive with copositivity in 12 of 17 cases (71%) and in one instance the IF finding was probably false positive. However, also for influenza A virus our IF findings were fully comparable with figures obtained by others who performed the conventional washing technique for preparation of exfoliated cells from nasopharyngeal secretions. General practitioners submitted samples from 65 patients, and RS virus and influenza A virus were identified in eleven and four cases respectively. The simplicity of preparation of cell smears from nasopharyngeal secretions with our simplified method opens up the possibility of the application of rapid respiratory virus diagnostic service to an increasing number of hospital departments and also for general practitioners. We feel that this method is a suitable tool for surveillance of certain respiratory virus infections.