Browsing by Author "Kalish, Jennifer M."

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    A dyadic approach to the delineation of diagnostic entities in clinical genomics
    (Cell Press, 2021-01-07) Biesecker, Leslie G.; Adam, Margaret P.; Alkuraya, Fowzan S.; Amemiya, Anne R.; Bamshad, Michael J.; Beck, Anita E.; Bennett, James T.; Bird, Lynne M.; Carey, John C.; Chung, Brian; Clark, Robin D.; Cox, Timothy C.; Curry, Cynthia; Palko Dinulos, Mary Beth; Dobyns, William B.; Giampietro, Philip F.; Girisha, Katta M.; Glass, Ian A.; Graham, John M., Jr.; Gripp, Karen W.; Haldeman-Englert, Chad R.; Hall, Bryan D.; Innes, A. Micheil; Kalish, Jennifer M.; Keppler-Noreuil, Kim M.; Kosaki, Kenjiro; Kozel, Beth A.; Mirzaa, Ghayda M.; Mulvihill, John J.; Nowaczyk, Malgorzata J.M.; Pagon, Roberta A.; Retterer, Kyle; Rope, Alan F.; Sanchez-Lara, Pedro A.; Seaver, Laurie H.; Shieh, Joseph T.; Slavotinek, Anne M.; Sobering, Andrew K.; Stevens, Cathy A.; Stevenson, David A.; Tan, Tiong Yang; Tan, Wen-Hann; Tsai, Anne C.; Weaver, David D.; Williams, Marc S.; Zackai, Elaine; Zarate, Yuri A.; Medical and Molecular Genetics, School of Medicine
    The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.
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    Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients
    (Wiley, 2018-08) Levin, Mark D.; Saitta, Sulagna C.; Gripp, Karen W.; Wenger, Tara L.; Ganesh, Jaya; Kalish, Jennifer M.; Epstein, Michael R.; Smith, Rosemarie; Czosek, Richard J.; Ware, Stephanie M.; Goldenberg, Paula; Myers, Angela; Chatfield, Kathryn C.; Gillespie, Matthew J.; Zackai, Elaine H.; Lin, Angela E.; Pediatrics, School of Medicine
    Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first-line supraventricular tachycardia anti-arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti-arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4-month-old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.
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    Response to Hamosh et al
    (Elsevier, 2021) Biesecker, Leslie G.; Adam, Margaret P.; Alkuraya, Fowzan S.; Amemiya, Anne R.; Bamshad, Michael J.; Beck, Anita E.; Bennett, James T.; Bird, Lynne M.; Carey, John C.; Chung, Brian; Clark, Robin D.; Cox, Timothy C.; Curry, Cynthia; Dinulos, Mary Beth Palko; Dobyns, William B.; Giampietro, Philip F.; Girisha, Katta M.; Glass, Ian A.; Graham, John M., Jr.; Gripp, Karen W.; Haldeman-Englert, Chad R.; Hall, Bryan D.; Innes, A. Micheil; Kalish, Jennifer M.; Keppler-Noreuil, Kim M.; Kosaki, Kenjiro; Kozel, Beth A.; Mirzaa, Ghayda M.; Mulvihill, John J.; Nowaczyk, Malgorzata J.M.; Pagon, Roberta A.; Retterer, Kyle; Rope, Alan F.; Sanchez-Lara, Pedro A.; Seaver, Laurie H.; Shieh, Joseph T.; Slavotinek, Anne M.; Sobering, Andrew K.; Stevens, Cathy A.; Stevenson, David A.; Tan, Tiong Yang; Tan, Wen-Hann; Tsai, Anne C.; Weaver, David D.; Williams, Marc S.; Zackai, Elaine; Zarate, Yuri A.; Medical and Molecular Genetics, School of Medicine