Browsing by Author "Rope, Alan F."

Now showing 1 - 4 of 4
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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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    Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15
    (Oxford University Press, 2019-05-01) Cheng, Hanyin; Gottlieb, Leah; Marchi, Elaine; Kleyner, Robert; Bhardwaj, Puja; Rope, Alan F.; Rosenheck, Sarah; Moutton, Sébastien; Philippe, Christophe; Eyaid, Wafaa; Alkuraya, Fowzan S.; Toribio, Janet; Mena, Rafael; Prada, Carlos E.; Stessman, Holly; Bernier, Raphael; Wermuth, Marieke; Kauffmann, Birgit; Blaumeiser, Bettina; Kooy, R Frank; Baralle, Diana; Mancini, Grazia M. S.; Conway, Simon J.; Xia, Fan; Chen, Zhao; Meng, Linyan; Mihajlovic, Ljubisa; Marmorstein, Ronen; Lyon, Gholson J.; Pediatrics, School of Medicine
    N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder. Additionally, some subjects present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. One of the individuals is an 11-year-old boy with a frameshift variant in exon 7 of NAA10, who presents most notably with microphthalmia, which confirms a prior finding with a single family with Lenz microphthalmia syndrome. Biochemical analyses of variants as part of the human NatA complex, as well as enzymatic analyses with and without the HYPK regulatory subunit, help to explain some of the phenotypic differences seen among the different variants.
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    Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15
    (Oxford University Press, 2020-03-27) Cheng, Hanyin; Gottlieb, Leah; Marchi, Elaine; Kleyner, Robert; Bhardwaj, Puja; Rope, Alan F.; Rosenheck, Sarah; Moutton, Sébastien; Philippe, Christophe; Eyaid, Wafaa; Alkuraya, Fowzan S.; Toribio, Janet; Mena, Rafael; Prada, Carlos E.; Stessman, Holly; Bernier, Raphael; Wermuth, Marieke; Kauffmann, Birgit; Blaumeiser, Bettina; Kooy, R. Frank; Baralle, Diana; Mancini, Grazia M. S.; Conway, Simon J.; Xia, Fan; Chen, Zhao; Meng, Linyan; Mihajlovic, Ljubisa; Marmorstein, Ronen; Lyon, Gholson J.; Medicine, School of Medicine
    In the original version of this article, Ezzat El-Akkad’s name was misspelled in the acknowledgements section; this has now been corrected. The authors apologize for this error.
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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