This article explores the career trajectory of Gabrielle Mediak, particularly her departure from News 4, and also delves into a genetic study concerning Matrix Gla Protein (MGP) and its implications for skeletal dysplasia.
Gabrielle Mediak's Departure from News 4
Gabrielle Mediak, a familiar face on News 4 as the reporter behind "Good News with Gabby," has announced her departure from the station. Mediak joined News 4 in January 2019, fulfilling a childhood dream of working at the station she grew up watching. Her segment, "Good News with Gabby," focused on highlighting positive stories within the community, a role she embraced with a deep sense of responsibility.
Mediak expressed her affection for Buffalo, emphasizing that her departure is not a permanent goodbye but rather a "see you later." She hinted at future plans, encouraging viewers to "stay tuned." Known for her extensive coverage of Western New York, Mediak was actively involved in the community, reporting from various towns and villages.
An update revealed that Mediak accepted a significant career opportunity as the main morning anchor in a larger market. While the specific city and television station remain undisclosed, it was mentioned that it is a Top 40 market.
Genetic Study on Matrix Gla Protein (MGP)
The article also references a genetic study focusing on Matrix Gla Protein (MGP), a vitamin K-dependent protein crucial for inhibiting extracellular matrix mineralization. Biallelic loss-of-function variants in the MGP gene are known to cause Keutel syndrome, a rare autosomal recessive disorder characterized by calcification of cartilage and vascular tissues.
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MGP and Skeletal Dysplasia
Skeletal dysplasias are a diverse group of genetic disorders affecting bone and cartilage development, leading to short stature and abnormal skeletal morphology. The study highlights four individuals from two unrelated families who presented with spondyloepiphyseal dysplasia and heterozygous variants in the MGP gene, specifically affecting residue Cys19.
MGP, a secreted protein, plays a vital role in preventing mineralization in vascular and cartilaginous tissues. It contains glutamic acid residues that undergo γ-carboxylation, a vitamin K-dependent process. Loss-of-function variants in MGP can result in Keutel syndrome (KS), characterized by cartilage and vascular tissue calcification, midfacial hypoplasia, pulmonary artery stenosis, brachytelephalangism, developmental delay, and hearing loss.
Study Findings and Mouse Models
The study investigated the cellular and molecular effects of a heterozygous variant (C19F) using cell and genetically modified mouse models. Mice expressing C19F MGP exhibited skeletal anomalies similar to those observed in affected individuals. The research suggests that endoplasmic reticulum stress-induced apoptosis of growth plate chondrocytes is the primary mechanism underlying the skeletal dysplasia.
Researchers created a "knock-in" mouse model to express the mutant protein and reproduce the spondyloepiphyseal dysplasia phenotype seen in affected individuals. The study demonstrated that impaired processing of the signal peptide in the mutated C19F MGP leads to its accumulation in the endoplasmic reticulum (ER). This accumulation causes ER stress and apoptosis of chondrocytes, disrupting normal endochondral bone development.
Clinical Presentation of Affected Individuals
Individuals with the MGP variants presented with a range of skeletal abnormalities. Individuals 1, 2, and 3 from Family 1 exhibited short stature with a disproportionately short trunk, short hands, mild midface retrusion, and epiphyseal anomalies. Individual 1, the 52-year-old mother, experienced progressive epiphyseal degeneration, requiring bilateral hip replacement at a young age. Individual 4 from Family 2 displayed short stature with a disproportionate short trunk, short hands, rhizomelia, exaggerated lumbar lordosis, midface retrusion, and epiphyseal anomalies.
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X-rays revealed diffuse platyspondyly with biconcavity of the vertebrae in all four affected individuals. Radiographs of the hands showed brachytelephalangism of the lesser digits. The pelvis was proportionate with capacious acetabuli, and ossification was irregular in skeletally immature patients. The lower extremities featured broad, flattened epiphyses of the femur and tibia. Coxa valga and genu valgum were also observed.
Genetic Analysis
Exome sequencing identified a heterozygous missense variant in MGP (NM000900.3:c.56G>T:p.C19F) shared among the affected individuals from Family 1. This variant is rare and predicted to impact protein structure and function. A de novo heterozygous missense variant in MGP (NM000900.3:c.56G>A:p.C19Y) was identified in Individual 4 from Family 2.
Mouse Model Generation and Phenotype
The researchers used CRISPR/Cas9-based mutagenesis to create a "knock-in" mouse model with the C19F variant. The presence of the desired variant was confirmed by PCR and Sanger sequencing. The mutant mice were initially normal at birth but exhibited reduced weight gain after two weeks of age. At six weeks of age, they displayed an overall shortening of body length compared to control mice. X-ray images revealed smaller skeletons with shorter vertebrae and decreased radio opacity. Femoral and tibial lengths were significantly shorter in mutant mice. Micro-CT analysis revealed craniofacial anomalies and abnormal calcification of tracheal cartilage.
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