A new mutation, 3905insT, accounts for 4.8% of 1173 CF chromosomes in Switzerland and causes a severe phenotype.

We have analysed 1173 cystic fibrosis (CF) chromosomes from Switzerland for eight mutations in the CF transmembrane conductance regulator (CFTR) gene. This permitted the identification of 88.5% of all mutations present. A novel insertion mutation in exon 20 of the CFTR gene, 3905insT, was discovered. This mutation accounted for 4.8% of CFTR gene mutations in Switzerland and has since been identified in other populations of probable Swiss descent. It is associated with a highly variable clinical phenotype but always with pancreatic insufficiency. Haplotype analysis with three intragenic microsatellites in the CFTR gene showed that the mutation is associated with a haplotype rarely identified on other CFTR alleles and, therefore, that the frequency of the mutation in Switzerland is explained by a founder effect of a relatively recent mutation event.

[Molecular genetics diagnosis of Steinert's myotonic dystrophy]. / Molekulargenetische Diagnose der myotonen Dystrophie Steinert.

Myotonic dystrophy (DM) is the most common neuromuscular disease with adult onset (incidence 1 in 8000). The biochemical basis of this autosomal dominantly inherited disease is still unknown. The most striking features are myotonia and progressive muscular wasting. There is high variability of disease severity in patients from different families, but also within the same family. For practical reasons three subtypes can be defined: The classical adult onset form of the disease, a mild form with late onset and/or very moderate symptoms, eg. cataracts only, and the most severe congenital form which is transmitted by affected females. Furthermore, the progression of DM in affected families may exhibit an increase in the severity of the disease in successive generations. This observation is called anticipation. Very recently the DM gene has been cloned and an unstable DNA sequence specific for the disease has been characterized. Detection of an enlarged DNA fragment due to the expansion of a trinucleotide (CTG) repeat within the DM gene can be used for direct DNA diagnosis in affected individuals and persons at risk. Furthermore, there is a strong correlation between the length of fragment expansion and the degree of disease severity in gene carriers. We report here our preliminary results of the investigation of over 70 patients and demonstrate the clinical usefulness of this new method by the findings in three families.

Insulin-like growth factors (IGF) 1 and 2 in human foetal plasma and relationship to gestational age and foetal size during midpregnancy.

IGF-1 and IGF-2 were measured by specific radioimmunoassay after acid-ethanol extraction of plasma obtained by foetoscopy from 20 normal foetuses aged 15-23 weeks. IGF-1 and IGF-2 levels were 36 +/- 11 and 162 +/- 55 ng/ml, respectively. In comparison, levels in cord blood were 84 +/- 58 and 264 +/- 176 ng/ml, respectively, and in adult plasma were 410 +/- 106 and 818 +/- 272 ng/ml. Both IGF-1 and IGF-2 were in the normal foetal range in a further three foetuses with anencephaly and two foetuses with spina bifida. No sex difference was observed. IGF-1 was positively correlated with foetal body weight (P less than 0.001), placenta weight (P less than 0.02) and with body length measured crown-rump (P less than 0.01) or crown-heel (P less than 0.02). No correlation between IGF-2 and body weight, length, placenta weight or gestational age was found. Both IGF-1 and IGF-2 are present in the human foetal circulation earlier in gestation than has previously been demonstrated, the levels being low throughout this period of gestation in comparison with adult plasma.