Infantile hypertrophic pyloric stenosis
Prem Puri in Newborn Surgery, 2017
Romeo et al.110 investigated dystroglycans and sarcoglycans, two proteins that, along with dystrophin, form the dystrophin–glycoprotein complex, which is important for maintaining the structural integrity and function of muscle fibers. They reported that although dystroglycans showed similar expressions in IHPS and controls, sarcoglycans were present in controls but absent in IHPS. It is suggested that lack of sarcoglycans can alter the physiology of SMCs and predispose to IHPS.
Carrier Screening For Inherited Genetic Conditions
Vincenzo Berghella in Obstetric Evidence Based Guidelines, 2022
Clinical features: This syndrome is caused by abnormal glycosylation of alpha-dystroglycan. This abnormal protein causes progressive weakness of skeletal muscles and abnormal migration of neurons. Affected individuals have hypotonia and can never walk. Cobblestone lissencephaly results in development and intellectual disability. Microphthalmia is also common. Most individuals do not survive past age 3.
Muscle Disorders
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
The dystrophin–glycoprotein complex includes the sarcoglycans and dystroglycans. It is discussed above under dystrophinopathies. Defects in sarcoglycans present as LGMD R3–R6. Mutations in FKRP, POMT1, and Fukutin disrupt the function of glycosyl transferases that are important for the posttranslational modification of alpha-dystroglycan in the DGC (Figure 27.1).
Restoration of dystrophin expression and correction of Duchenne muscular dystrophy by genome editing
Published in Expert Opinion on Biological Therapy, 2021
Tejal Aslesh, Esra Erkut, Toshifumi Yokota
In spite of using AAV vectors in vivo in animal models, several issues need to be addressed before employing AAVs for delivering the CRISPR components to DMD patients. The most important concern is preexisting antibodies against AAV vectors in some patients, generating an immune reaction. Considering the immunogenicity risks, AAVs are often administered in a single tolerated dose. Gene replacement clinical trials involving the AAV administration of a microdystrophin transgene have shown no adverse or immunogenic effects associated with the viral vector; corticosteroids were administered to prevent any immune response, as necessary (NCT03375164) [88]. The microdystrophin includes the N-terminus for binding to actin, SLRs that bind to the sarcolemma and microtubule, and the cysteine-rich domain which binds to β-dystroglycan, thereby restoring the structural integrity of dystrophin-associated protein complex (DAPC) [88]. This gives gene replacement an edge over genome editing which may not necessarily result in a corrected protein structure. Careful consideration is required to ensure that genomic deletion results in both the restoration of the reading frame along with the structure and phasing of the SLRs of the dystrophin protein.
B4GAT1 Gene Associated Congenital Muscular Dystrophy Presenting with Recurrent Severe Ventriculomegaly: Case Report and Review of Literature
Published in Fetal and Pediatric Pathology, 2022
Meenakshi Lallar, Ladbans Kaur, Meetan Preet, U. P. Singh
Dystrophinopathies are genetic diseases that can present with variable phenotypes ranging from severe prenatal ventriculomegaly to postnatal childhood-onset muscle weakness. Each cell has a dystrophin protein–glycoprotein complex (DGC) which forms a link between the cytoskeleton and the extracellular matrix. The modification of dystrophin protein to attach glycoprotein is mediated by enzymes called glycosyltransferases. This modification makes this DGC complex sticky, so it can bind to the components of the extracellular matrix. Defective glycosylation due to abnormality of these enzymes leads to loss of dystroglycan binding ability, which is critical for the function of many tissues, especially muscle and brain and causes congenital muscular dystrophies, a group of diseases that are characterized by a progressive loss of muscle function.
An update on diagnostic options and considerations in limb-girdle dystrophies
Published in Expert Review of Neurotherapeutics, 2018
Corrado Angelini, Laura Giaretta, Roberta Marozzo
IHC analysis may provide a clear and highly specific result in sarcoglycanopathy, dysferlinopathy, telethoninopathy, plectinopathy where a severely reduced or absent labeling for sarcoglycan, dysferlin, telethonin, or plectin, respectively, appears to be a highly specific disease marker. In sarcoglycanopathies, the reduction in all or many of the sarcoglycan complex members, caused by their interdependence, may complicate the identification of the primary genetic defect. Since sarcoglycanopathies usually show an absence of all four sarcoglycan proteins, a screening can be done with alpha-sarcoglycan, an absence of alpha-sarcoglycan is found together with this particular defect associated with the other nonmutated sarcoglycans. In dystroglycanopathies, a secondary reduction of laminin alpha2 and of the glycosylated epitope of alpha-dystroglycan may be seen, reflecting the common pathological feature of disorders. The degree of reduction is variable in LGMD due to dystroglycanopathy: it is due to dystroglycan glycosylation defect that may be absent in an unequivocal or subtle way, and the relative expression seems proportional to the clinical severity.