Although the function of FKRP is unknown, FKRP has been suggested to be a Golgiresident protein and to be involved in the glycosylation of α-dystroglycan as a glycosyltransferase or a kind

of modulator. A recent study described a patient with congenital muscular dystrophy, profound mental retardation, white matter changes, and subtle structural abnormalities in the brain and a Inhibitors,research,lifescience,medical reduction of immunologically detectable α-dystroglycan. The patient was found to have this website mutations in the LARGE gene. This type of muscular dystrophy was named MDC1D. Since multiple genes are known to cause α-dystroglycanopathies, with an extremely broad clinical spectrum and relatively poor phenotype-genotype correlation, at present molecular diagnosis of α-dystroglycanopathy patients is difficult and requires searching for mutations gene by gene. These methods are expensive and time-consuming. At present, of the six known Inhibitors,research,lifescience,medical α-dystroglycanopathy genes, the function of the protein product is clear only for POMT1, POMT2 and POMGnT1 (25).

Vajsar et al. and we have developed assay methods for lymphoblast POMGnT1 (29, 30) and POMT activity (29, 30), respectively, for patients with confirmed α-dystroglycanopathy. To screen patients with suspected forms Inhibitors,research,lifescience,medical of α-dystroglycanopathy, we measured the activities of both POMT and POMGnT1 in lymphoblasts from a series of patients (29, 30). We observed reductions in POMGnT1 or POMT activity in several uncharacterized patients, in whom secondary targeted sequencing led to the identification of mutations in POMT1, POMT2 or POMGnT1. Inhibitors,research,lifescience,medical This lymphoblast-based assay was proposed as a rapid and relatively simple diagnostic test for MEB and WWS patients, and may bypass the need for invasive muscle biopsies when clinical findings are highly suggestive of an α-dystroglycanopathy. It is noteworthy that patients with FKRP mutations did not show reduced activity

for POMT and POMGnT1, suggesting that FKRP is not associated with POMT1 or POMT2, or with Inhibitors,research,lifescience,medical POMGnT1 (30). Recently, FKRP was reported to be associated with the sarcolemmal dystrophin-glycoprotein complex and may influence the glycosylation of α-dystroglycan, although the precise function of FKRP remains unknown (31). On the other hand, fukutin was reported to be associated with POMGnT1 in the Golgi Idoxuridine compartment (Fig. ​(Fig.1)1) (32). Although fukutin has no proven glycosyltransferase activity, transgenic knock-in mouse carrying a retrotransposon insertion in the fukutin gene showed a 30% reduction of POMGnT1 activity (32), suggesting that fukutin modulates POMGnT1 activity in muscle. It will be interesting to test POMGnT1 activity in muscle, lymphoblasts, and fibroblasts from FCMD patients to determine whether mutations in the fukutin gene could modulate POMGnT1 activity. Perspectives In summary, O-mannosylation is important in muscle and brain development.