Mutations of the CFTR gene and the 5T genotype are associated with chronic pancreatitis.

A genetic register for von Hippel-Lindau disease was set up in the north west of England in 1990.

Background-Polymorphisms in transforming growth factor (TGF)-1 associated with variations in cytokine levels are linked to fibrosis in a number of tissues. However, the contribution of this cytokine to organ fibrosis in patients with cystic fibrosis is presently unclear. This study was undertaken to examine the association between TGF-1 gene polymorphisms and the development of pulmonary dysfunction in patients with cystic fibrosis. Methods-Polymorphisms in the TGF-1 gene defining amino acids of codons 10 and 25 were determined by ARMS-PCR using DNA stored on 171 Caucasian patients who were homozygous for the F508 mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical information on the patients was obtained from medical records. Results-Patients with cystic fibrosis of a TGF-1 high producer genotype for codon 10 had more rapid deterioration in lung function than those with a TGF-1 low producer genotype. The relative risk of accelerated decline in forced expiratory volume in one second (FEV 1 ) to 50% predicted and forced vital capacity (FVC) to 70% predicted of patients with a high producer genotype was 1.74 (95% CI 1.11 to 2.73) compared with 1.95 (95% CI 1.24 to 3.06) for those with a low producer genotype. Discussion-TGF-1 genotypes may have a role in mediating pulmonary dysfunction in patients with cystic fibrosis. Further work is required to determine whether inhibition of TGF-1 activity in these patients may slow disease progression. (Thorax 2000;55:459-462)

No abstract

32 families informative for the segregation of Tuberous sclerosis (TSC) have been examined for genetic markers on chromosomes 9, 11, 12 and 16. In one large family there was clear evidence of linkage to markers on chromosome 16p13.3 (lodscore with D16S291 of 4.7 at theta = 0) but other families were too small to give individually convincing lodscores. Combined results for all families gave positive results with ABO/DBH on chromosome 9 (max lod 2.63) and with D16S291 on chromosome 16 (max lod 3.98) at values of theta of 0.2 in each case. Further analysis showed strong evidence for heterogeneity with approximately half the families linked to a locus TSC1 on chromosome 9 between ASS and D9S298 and half to TSC2 on chromosome 16 close to D16S291. There was no definite support for a third locus although in many families this could not be excluded. In three families the segregation pattern of TSC remains unexplained. In two of these the family apparently segregates for TSC1 but in each case a single affected individual appeared to exclude the whole of the candidate region. Preliminary analysis of clinical features did not reveal any definite differences in incidence of mental handicap between individuals in different linkage groups or with different sex of the parent of origin. The frequencies of periungual fibromas and facial angiofibromas were also similar in both linkage groups. The difficulties of detecting linkage in small families where there is locus heterogeneity are discussed. The program ZZ was found to be helpful in this respect.