In keeping with the hypothesis of a common pathogenetic pathway, allelic mutations of any of these genes results in conditions of variable severity broadly correlated with the degree of ADG hypoglycosylation. Molecular genetic PH-797804 supplier analysis of patients with a dystroglycanopathy therefore should include all these 6 genes; however, approximately 35% of patients have no identifiable mutations, Inhibitors,research,lifescience,medical strongly pointing towards further genetic heterogeneity. Genetic analysis suggests that the possibility of a single major locus accounting for the remaining dystroglycanopathies

is unlikely and we must be prepared to search for multiple genes associated with the glycosylation of ADG. Acknowledgement

The authors wish to thank the ENMC CMD consortium Inhibitors,research,lifescience,medical for the ongoing collaboration. The financial support of the Muscular Dystrophy Campaign and of the Department of Health (NCG) is gratefully acknowledged. The group at Guy’s Hospital Trust London involved in the NCG diagnostic work (Dr Stephen Abbs; Mrs Rachael Mein; Miss Judith Pagan) is also gratefully acknowledged.

This very rare disease has a frequency estimated at 1 in 8 million births. This, however, seems to be underestimated due to misdiagnosed or non-recognized cases and could Inhibitors,research,lifescience,medical be 1 in 4 million. The disease affects mainly Caucasians, slightly more boys (M:F = 1.5:1). HGPS is a multisystem disorder affecting

various organs – muscles, bones, skin, subcutaneous Inhibitors,research,lifescience,medical tissue, heart, etc. The classic symptoms are: short stature, bird-like faces, cranio-facial disproportion, baked beak nose, micrognathia, graying sparse hair, wrinkled tight skin with pigmentation and prominent vessels, in some cases scleroderma-like indurations, pear-shaped thorax, coxa valga, short clavicles, joint contractures, osteolysis of distal phalanges Inhibitors,research,lifescience,medical of fingers, delayed dentition, cataract (Fig. ​(Fig.1).1). Early atherosclerosis, leading to heart infarction or stroke is the main cause of death. Very characteristic is low weight and delayed growth. IQ is usually normal, no brain changes have been described (3–7). Figure 1 Hutchinson-Gilford progeria (from CYTH4 collection of prof. S. Jablońska). Most of these symptoms mentioned appear between 6 and 18 months of life, at birth the child is usually considered to be normal. The mean life-span in typical cases is estimated at about 11 years, but single older cases (even > 20 years old) with confirmed diagnosis have been reported (9). Most of the cases reported so far (no more than ± 110) were sporadic, products of consanguineous parents. The mode of transmission, according to most authors, is autosomal dominant (AD). In a few cases, the mode of transmission was autosomal recessive (10, 11). The risk of recurrence is estimated as lower than 3%.