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The molecular basis of myotonic dystrophy (DM) has been characterised. All DM mutations characterised to date appear as an unstable elongation of a fragment containing a tandem repeat of a CTG motif, which can be visualised in both EcoRI and BamHI digests. It has been shown that the fragment is polymorphic in the normal population. Another 1 kb insertion/deletion polymorphism located near the unstable CTG repeat region has been identified. The 1 kb insertion allele is present in all DM patients. These different polymorphic systems can be distinguished using cDNA25 and BamHI, because this enzyme cuts between the site of the 1 kb insertion and the CTG repeat. We thus haplotyped DM patients from 72 French families and clearly showed that all chromosomes (100%) with the DM mutation carried the 1 kb insertion as well. In addition to this association, we detected significant linkage disequilibrium between the DM locus and D19S63 for which allelic frequencies were different from other European populations. Our results in the French DM population are thus in agreement with the hypothesis that the CTG expansion occurred on one or a few ancestral chromosomes carrying the large 1 kb insertion allele.

International audience; Background: Our discovery in 2003 of the first mutations of PCSK9 gene causing autosomal dominant hypercholesterolaemia (ADH) shed light on an unknown factor that strongly influences the level of circulating low density lipoprotein cholesterol (LDL-C). PCSK9 gain of function mutations cause hypercholesterolaemia by a reduction of LDL receptor levels, while PCSK9 loss of function variants are associated with a reduction of LDL-C values and a decreased risk of coronary heart disease. METHODS AND RESULTS: We report an insertion of two leucines (p.L21tri also designated p.L15_L16ins2L) in the leucine stretch of the signal peptide of PCSK9 that is found in two of 25 families with familial combined hyperlipidaemia (FCHL). This mutant is associated with high total cholesterol and LDL-C values in these families and is found also in a patient with familial hypercholesterolaemia and her father. CONCLUSION: PCSK9 variants might contribute to FCHL phenotype and are to be taken into consideration in the study of this complex and multigenic disease with other genes implicated in dyslipidaemia.