Congenital muscular dystrophies with Alterations in the glycosylation or dystroglycanopathy, consistes in an inherited disorder that affects the metabolism of glycoproteins and other glycoconjugates, resulting in errors in the synthesis of glycans.
Characteristics associated with the disease are the presence of cognitive deterioration and a slight delay, changes in the structure of the brain and / or eyes, seizures, and in some cases exercise intolerance. Due to the wide phenotypic spectrum of pathology, certain syndromes were described initially like dystroglycanopathies, as in the case of Walker Warburg syndrome, disease muscle-eye-brain, Fukuyama congenital muscular dystrophy and congenital muscular dystrophy type 1C and 1D.
Mutations have been detected in various genes associated with the presence of dystroglycanopathies, causing a defect in the protein alpha-dystroglycan. Specifically, genes ISPD (7p21.2), POMT1 (9q34.13) POMT2 (14q24.3) POMNGT1 (1p34.1), FKTN (9q31.2), FKRP (19q13.32) and LARGE ( 22q12.3). The proteins encoded by these genes share a common destiny: they participate at critical moments involved in the synthesis of glycan chains of alpha-dystroglycan, and in the O-mannosylation.
Currently it has been observed a wide phenotypic variability, so a gene is not directly associated to a single syndrome. However, certain shortcomings have been able to link to certain genes, more specifically. FKRP, POMT1 and FKTN genes are associated with cardiac disorders. However, POMT2 and POMT1 are linked to the occurrence of microcephaly. POMGNT1 is associated with the presence of macrocephaly and epilepsy.
Dystroglycanopathies have been diagnosed based on the observation of signs and symptoms that accompany the disease, together with analysis of biochemical markers. However, molecular genetic diagnosis are an especially useful tool for the early detection of the disease. Bioarray has a complete NGS panel that includes the genes mentioned above, whose alterations are linked to dystroglycanopathies.