CCN1 mutation is associated with atrial septal defect

The genetic basis of congenital heart disease remains unknown in most of the cases. Recently, a novel mouse model shed new light on the role of CCN1/CYR61, a matricellular regulatory factor, in cardiac morphogenesis. In a candidate gene approach, we analyzed a cohort of 143 patients with atrial septal defects (ASD) by sequencing the coding exons of CCN1. In addition to three frequent polymorphisms, we identified an extremely rare novel heterozygous missense mutation (c.139C > T; p.R47W) in one patient with severe ASD. The mutation leads to an exchange of residues with quite different properties in a highly conserved position of the N-terminal insulin-like growth factor binding protein module. Further bioinformatic analysis, exclusion of known ASD disease genes as well as the exclusion of the mutation in a very high number of ethnically matched controls (more than 1,000 individuals) and in public genetic databases, indicates that the p.R47W variant is a probable disease-associated mutation. The report about ASD in mice in heterozygous Ccn 1 +/- animals strongly supports this notion. Our study is the first to suggest a relationship between a probable CCN1 mutation and ASD. Our purpose here was to draw attention to CCN1, a gene that we believe may be important for genetic analysis in patients with congenital heart disease

Linkage mapping of the bovine lysosomal alphamannosidase (MANB) gene

Lysosomal alpha-mannosidase is involved in the metabolism of mannoses in oligosaccharides in lysosomes. Deficiency of alpha-mannosidase, alpha-mannosidosis, has been described as an autosomal recessive storage disease in angus cattle, Galloway cattle and in cats. It is caused by non-synonymous substitutions in the encoding gene (MANB). Primers for MANB were designed from a bovine sequence (Gen Bank accession number U97686) and amplified a 316-bp fragment comprising intron 2 and adjacent exonic sequences. This paper discusses PCR primers, PCR conditions and polymorphism detection; and allele frequencies, inheritance and chromosomal location

Genomic DNA differences between pathogenic and nonpathogenic Entamoeba histolytica

DNA libraries were constructed from pathogenic (HM-1:IMSS) and nonpathogenic (SAW 1734) isolates of Entamoeba histolytica. A cDNA clone (cEH-P1) specific for pathogenic amoebae was identified by screening with a pool of sera from patients with invasive amoebiasis that had been absorbed with nonpathogenic amoebae. This clone was used for the identification of a homologous clone (cEH-NP1) in the cDNA from nonpathogenic amoebae. Sequence analysis and comparison of the predicted amino acid sequences for both clones disclosed 12% evolutionary divergence in structure. Hybridization of both cDNA probes to genomic DNA from four pathogenic and five nonpathogenic E. histolytica isolates revealed two distinct Southern blot patterns, one characteristic for pathogenic amoebae and the other for nonpathogenic amoebae. Further, the complex pattern of restriction fragments hybridizing to an actin cDNA probe was also different between pathogenic and nonpathogenic isolates but was conserved within each g roup of amoebae. The results indicate that pathogenic isolates of E. histolytica are genetically distinct from nonpathogenic isolates

Allergy to methyltetrahydrophthalic anhydride in epoxy resin workers

One hundred and forty four current and 26 former workers in a plant producing barrels for rocket guns from an epoxy resin containing methyltetrahydrophthalic anhydride (MTHPA; time weighted average air concentration up to 150 uglm') were studied. They showed higher frequencies of work related symptoms from the eyes (31 v 0%; p < 0-001), nose (53 v 9%; p < 0-001), pharynx (26 v 6%; p < 0-01), and asthma (11 v 0%; p < 0 05) than 33 controls. Also they had higher rates of positive skin prick test to a conjugate of MTHPA and human serum albumin (16 v 0%; p < 0-01), and more had specific IgE and IgG serum antibodies (18 v 0%; p < 0-01 and 12 v 0%; p < 0 05 respectively). There were statistically significant exposure-response relations between exposure and symptoms from eyes and upper airways, dry cough, positive skin prick test, and specific IgE and IgG antibodies. There was a non-significant difference in reaction to metacholine between exposed workers and non-smoking controls. In workers with and without specific IgE antibodies, differences existed in frequency of nasal secretion (54 v 23%; p < 0-05) and dry cough (38 v 12%; p < 0-05). Workers with specific IgG had more dry cough (38 v 12%; p < 0-05), but less symptoms ofnon-specific bronchial hyperreactivity (0 v 26%; p < 0-05). Atopic workers sneezed more than non-atopic workers (65 v 30%; p < 0-01). In a prospective study five sensitised workers who left the factory became less reactive to metacholine, and became symptom free. In 41 workers who stayed, there was no improvement, despite a 10-fold reduction in exposure. The results show the extreme sensitising properties ofMTHPA