Browsing by Author "Jin, Jay J."

Now showing 1 - 3 of 3
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    Clinical, immunological features, treatments, and outcomes of autoimmune hemolytic anemia in patients with RAG deficiency
    (American Society of Hematology, 2024) Wang, Chen; Sun, Bijun; Wu, Kevin; Farmer, Jocelyn R.; Ujhazi, Boglarka; Geier, Christoph B.; Gordon, Sumai; Westermann-Clark, Emma; Savic, Sinisa; Secord, Elizabeth; Sargur, Ravishankar; Chen, Karin; Jin, Jay J.; Dutmer, Cullen M.; Kanariou, Maria G.; Adeli, Mehdi; Palma, Paolo; Bonfim, Carmem; Lycopoulou, Evangelia; Wolska-Kusnierz, Beata; Dbaibo, Ghassan; Bleesing, Jack; Moshous, Despina; Neven, Benedicte; Schuetz, Catharina; Geha, Raif S.; Notarangelo, Luigi D.; Miano, Maurizio; Buchbinder, David K.; Csomos, Krisztian; Wang, Wenjie; Wang, Ji-Yang; Wang, Xiaochuan; Walter, Jolan E.; Pediatrics, School of Medicine
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    DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders
    (Elsevier, 2025) Lessel, Ivana; Baresic, Anja; Chinn, Ivan K.; May, Jonathan; Goenka, Anu; Chandler, Kate E.; Posey, Jennifer E.; Afenjar, Alexandra; Averdunk, Luisa; Bedeschi, Maria Francesca; Besnard, Thomas; Brager, Rae; Brick, Lauren; Brugger, Melanie; Brunet, Theresa; Byrne, Susan; de la Calle-Martín, Oscar; Capra, Valeria; Cardenas, Paul; Chappé, Céline; Chong, Hey J.; Cogne, Benjamin; Conboy, Erin; Cope, Heidi; Courtin, Thomas; Deb, Wallid; Dilena, Robertino; Dubourg, Christèle; Elgizouli, Magdeldin; Fernandes, Erica; Fitzgerald, Kristi K.; Gangi, Silvana; George-Abraham, Jaya K.; Gucsavas-Calikoglu, Muge; Haack, Tobias B.; Hadonou, Medard; Hanker, Britta; Hüning, Irina; Iascone, Maria; Isidor, Bertrand; Järvelä, Irma; Jin, Jay J.; Jorge, Alexander A. L.; Josifova, Dragana; Kalinauskiene, Ruta; Kamsteeg, Erik-Jan; Keren, Boris; Kessler, Elena; Kölbel, Heike; Kozenko, Mariya; Kubisch, Christian; Kuechler, Alma; Leal, Suzanne M.; Leppälä, Juha; Luu, Sharon M.; Lyon, Gholson J.; Madan-Khetarpal, Suneeta; Mancardi, Margherita; Marchi, Elaine; Mehta, Lakshmi; Menendez, Beatriz; Morel, Chantal F.; Moyer Harasink, Sue; Nevay, Dayna-Lynn; Nigro, Vincenzo; Odent, Sylvie; Oegema, Renske; Pappas, John; Pastore, Matthew T.; Perilla-Young, Yezmin; Platzer, Konrad; Powell-Hamilton, Nina; Rabin, Rachel; Rekab, Aisha; Rezende, Raissa C.; Robert, Leema; Romano, Ferruccio; Scala, Marcello; Poths, Karin; Schrauwen, Isabelle; Sebastian, Jessica; Short, John; Sidlow, Richard; Sullivan, Jennifer; Szakszon, Katalin; Tan, Queenie K. G.; Undiagnosed Diseases Network; Wagner, Matias; Wieczorek, Dagmar; Yuan, Bo; Maeding, Nicole; Strunk, Dirk; Begtrup, Amber; Banka, Siddharth; Lupski, James R.; Tolosa, Eva; Lessel, Davor; Medical and Molecular Genetics, School of Medicine
    BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. It is likely that gene-disruptive BCL11B variants and missense variants affecting zinc-binding cysteine and histidine residues cause mild to moderate neurodevelopmental delay with increased propensity for behavioral and dental anomalies, allergies and asthma, and reduced type 2 innate lymphoid cells. Missense variants within C2H2-ZnF DNA-contacting α helices cause highly variable clinical presentations ranging from multisystem anomalies with demise in the first years of life to late-onset, hyperkinetic movement disorder with poor fine motor skills. Those not in direct DNA contact cause a milder phenotype through reduced, target-specific transcriptional activity. However, missense variants affecting C2H2-ZnFs, DNA binding, and "specificity residues" impair BCL11B transcriptional activity in a target-specific, dominant-negative manner along with aberrant regulation of alternative DNA targets, resulting in more severe and unpredictable clinical outcomes. Taken together, we suggest that the phenotypic severity and variability is largely dependent on the DNA-binding affinity and specificity of altered BCL11B proteins.
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    Management of food allergy in the school setting
    (OceanSide, 2020-09-01) Huddleston, Christina M.; Kloepfer, Kirsten M.; Jin, Jay J.; Vitalpur, Girish V.; Pediatrics, School of Medicine
    Food allergy is a growing health and safety concern that affects up to 8% of school-age children. Because children spend a significant part of their day in school, and the overall number of school-age children with food allergy has been increasing, management of food allergies relies on the collaboration of allergists, families, and schools to treat and prevent acute allergic reactions. For schools, this involves policies centered on food allergen avoidance, preparedness with epinephrine autoinjectors, adequate school personnel training, and accommodations for an equal opportunity learning environment. Partnerships with allergists, primary care providers, students, families, school nurses, and school staff are vital for creating individualized and effective care plans that will allow all children, including those with food allergies, a safe and nurturing learning environment.