Muscle-eye-brain disease (MEB)

Gènes impliqués dans les alpha-dystroglycanopathies

“…Celles-ci jouent un impliquées dans l'ajout d'un résidu N-acétyglucosaminyl par liaison 1-2 pour POMGNT1 dans le cis-Golgi (cores M1 et M2 ; Figures 1A et 1B) [17] ou par liaison 1-4 dans le réticulum endoplasmique pour POMGNT2 (core M3 ; Figure 1C) [7]. Le gène POMGNT1 est le gène historique des MEBD identifié initialement dans la population finlandaise [18]. Il est également impliqué dans des cas de LISII foetale [2].…”

Alpha-Dystroglycanopathy

“…In contrast, both MEB and FCMD show striking founder effects. MEB was first described in Finland, where it is most prevalent, owing to a strong founder effect following by genetic drift (Santavuori et al, 1989, Haltia et al, 1997. Consequently, most MEB patients have come from a small, geographically isolated population in Finland, with few Caucasian exceptions.…”

“…The brain abnormalities are described as cobblestone lissencephaly; available pathological studies have demonstrated breeches of the glia limitans and over-migration of cortical neurons into the pial spaces. In WWS, the lifespan of patients is severely reduced and brain and eye abnormalities extremely severe (Dobyns et al, 1989); MEB and FCMD patients generally survive beyond infancy, ocular manifestations are usually milder in FCMD than in MEB (Fukuyama et al, 1981, Santavuori et al, 1989. To date, mutations in six genes which encode putative or confirmed glycosyltransferases have been identified in these autosomal recessively inherited disorders: Protein-O-mannosyl transferase 1 and 2 (POMT1 and POMT2), Protein-O-mannose 1,2-Nacetylglucosaminyltransferase 1 (POMGnT1), Fukutin-related protein (FKRP), Fukutin (FKTN), and LARGE.…”

Human genetic deficits in glycan formation.

“…MEB is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and brain malformation (type II lissencephaly). 44) Patients with MEB show severe cerebral and ocular anomalies, but some patients reach adulthood. MEB has been observed mainly in Finland.…”

“…In MEB, the cerebral and ocular anomalies are also severe, but some patients reach adulthood. 44), 53) The difference of severity between the two diseases may be explained as follows: If POMGnT1, which is responsible for the formation of the GlcNAcβ1-2Man linkage of O-mannosyl glycans, 30) is non-functional, only O-mannose residues may be present on α-dystroglycan in MEB. On the other hand, POMT1 mutations cause complete loss of O-mannosyl glycans in WWS.…”