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Carrier Screening For Inherited Genetic Conditions
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Whitney Bender, Lorraine Dugoff
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
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Kourosh Rezania, Peter Pytel, Betty Soliven
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).
Muscle, Bone, and Skin Disorders
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
Important insights have been gained in the structure and function of the 43K and 156K dystrophin-associated glycoproteins (DAGs), termed dystroglycans. Absence of dystrophin in DMD leads to the loss of dystroglycans that bind muscle fibers to the extracellular matrix (laminin), this disruption accounting for the eventual muscle cell necrosis.
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
Alpha dystroglycanopathies (aDG) are a group of muscular dystrophies with deficient glycosylation of alpha-dystroglycan (α-DG).To date, 18 genes have been associated with alpha dystroglycanopathy. The phenotypes associated with these genes range in presentation and severity. At the most severe end of the spectrum are the severe congenital muscular dystrophies (CMD) with brain and eye abnormalities (includes Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama CMD). The intermediate severity examples are CMD with or without intellectual disability and the milder phenotypes present as limb-girdle muscular dystrophy [2]. To date, there is no clear genotype-phenotype correlation. One recently discovered α-DG gene is B4GAT1 (previously called B3GNT1) where only two families with varying phenotypes have been reported to date [3–5].
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.
Fetal Presentation of Walker-Warburg Syndrome with Compound Heterozygous POMT2 Missense Mutations
Published in Fetal and Pediatric Pathology, 2023
Silvia Zago, Evelina Silvestri, Tiziana Arcangeli, Marina Calisesi, Chiara Romeo, Giulia Parmeggiani, Elena Parrini, Valentina Cetica, Renzo Guerrini, Andrea Palicelli, Maria Paola Bonasoni
The dystroglycan (DG) adhesion complex is made of two subunits: the extracellular and highly glycosylated α-DG and the transmembrane β-DG. α-DG mainly interacts with laminin facilitating the stability of the basement membrane, while β-DG represents a connection between the extracellular matrix and the cytoskeleton, including dystrophin. DG is the major non-integrin cell-adhesion complex and plays a key role in stabilizing various tissues at the cellular level: brain, including the blood-brain-barrier, peripheral nervous system, the neuromuscular junction, skeletal and smooth muscle [2].