Résumé
Marinesco-Sjögren syndrome (MSS), first described in 1931, is an autosomal recessive condition characterised by somatic and mental retardation, congenital cataracts and cerebellar ataxia. Progressive myopathy was later reported to be also a cardinal sign of MSS, with myopathic changes on muscle biopsies. Hypergonadotrophic hypogonadism and skeletal deformities related to pronounced hypotonia were also reported. The major differential diagnosis of MSS is the syndrome defined by congenital cataracts, facial dysmorphism and peripheral neuropathy (CCFDN), which is localised to 18qter. Using homozygosity mapping strategy in two large consanguineous families of Turkish and Norwegian origin, respectively, we have identified the MSS locus on chromosome 5q31. LOD score calculation, including the consanguinity loops, gave a maximum value of 2.9 and 5.6 at theta=0 for the Turkish and the Norwegian families, respectively, indicating linkage between the disease and the D5S1995-D5S436 haplotype spanning a 9.3 cM interval. Patients of the two families presented with the strict clinical features of MSS. On the other hand, the study of two smaller French and Italian families, initially diagnosed as presenting an atypical MS syndrome, clearly excluded linkage from both the MSS locus on 5q31 and the CCFDN locus in 18qter. Patients of the two excluded families had all MSS features (but the myopathic changes) plus peripheral neuropathy and optic atrophy, and various combinations of microcornea, hearing impairment, seizures, Type I diabetes, cerebral atrophy and leucoencephalopathy, indicating that only the pure MSS syndrome is a homogeneous genetic entity.