Browsing by Author "Seaver, Laurie H."

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    Correction to: De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome
    (Biomed Central, 2019-03-25) Vetrini, Francesco; McKee, Shane; Rosenfeld, Jill A.; Suri, Mohnish; Lewis, Andrea M.; Nugent, Kimberly Margaret; Roeder, Elizabeth; Littlejohn, Rebecca O.; Holder, Sue; Zhu, Wenmiao; Alaimo, Joseph T.; Graham, Brett; Harris, Jill M.; Gibson, James B.; Pastore, Matthew; McBride, Kim L.; Komara, Makanko; Al-Gazali, Lihadh; Al Shamsi, Aisha; Fanning, Elizabeth A.; Wierenga, Klaas J.; Scott, Daryl A.; Ben-Neriah, Ziva; Meiner, Vardiella; Cassuto, Hanoch; Elpeleg, Orly; Lloyd Holder Jr, J.; Burrage, Lindsay C.; Seaver, Laurie H.; Van Maldergem, Lionel; Mahida, Sonal; Soul, Janet S.; Marlatt, Margaret; Matyakhina, Ludmila; Vogt, Julie; Gold, June-Anne; Park, Soo-Mi; Varghese, Vinod; Lampe, Anne K.; Kumar, Ajith; Lees, Melissa; Holder-Espinasse, Muriel; McConnell, Vivienne; Bernhard, Birgitta; Blair, Ed; Harrison, Victoria; Muzny, Donna M.; Gibbs, Richard A.; Elsea, Sarah H.; Posey, Jennifer E.; Bi, Weimin; Lalani, Seema; Xia, Fan; Yang, Yaping; Eng, Christine M.; Lupski, James R.; Liu, Pengfei; Medical and Molecular Genetics, School of Medicine
    It was highlighted that the original article [1] contained a typographical error in the Results section. Subject 17 was incorrectly cited as Subject 1. This Correction article shows the revised statement. The original article has been updated.
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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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    Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5
    (Elsevier, 2014-05-01) McMillin, Margaret J.; Beck, Anita E.; Chong, Jessica X.; Shively, Kathryn M.; Buckingham, Kati J.; Gildersleeve, Heidi I.S.; Aracena, Mariana I.; Aylsworth, Arthur S.; Bitoun, Pierre; Carey, John C.; Clericuzio, Carol L.; Crow, Yanick J.; Curry, Cynthia J.; Devriendt, Koenraad; Everman, David B.; Fryer, Alan; Gibson, Kate; Uzielli, Maria Luisa Giovannucci; Graham, John M. Jr.; Hall, Judith G.; Hecht, Jacqueline T.; Heidenreich, Randall A.; Hurst, Jane A.; Irani, Sarosh; Krapels, Ingrid P.C.; Leroy, Jules G.; Mowat, David; Plant, Gordon T.; Robertson, Stephen P.; Schorry, Elizabeth K.; Scott, Richard H.; Seaver, Laurie H.; Sherr, Elliott; Splitt, Miranda; Stewart, Helen; Stumpel, Constance; Temel, Sehime G.; Weaver, David D.; Whiteford, Margo; Williams, Marc S.; Tabor, Holly K.; Smith, Joshua D.; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.; Medical & Molecular Genetics, School of Medicine
    Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher’s exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.
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    De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome
    (BMC, 2019-02-28) Vetrini, Francesco; McKee, Shane; Rosenfeld, Jill A.; Suri, Mohnish; Lewis, Andrea M.; Nugent, Kimberly Margaret; Roeder, Elizabeth; Littlejohn, Rebecca O.; Holder, Sue; Zhu, Wenmiao; Alaimo, Joseph T.; Graham, Brett; Harris, Jill M.; Gibson, James B.; Pastore, Matthew; McBride, Kim L.; Komara, Makanko; Al-Gazali, Lihadh; Al Shamsi, Aisha; Fanning, Elizabeth A.; Wierenga, Klaas J.; Scott, Daryl A.; Ben-Neriah, Ziva; Meiner, Vardiella; Cassuto, Hanoch; Elpeleg, Orly; Holder, J. Lloyd, Jr.; Burrage, Lindsay C.; Seaver, Laurie H.; Van Maldergem, Lionel; Mahida, Sonal; Soul, Janet S.; Marlatt, Margaret; Matyakhina, Ludmila; Vogt, Julie; Gold, June-Anne; Park, Soo-Mi; Varghese, Vinod; Lampe, Anne K.; Kumar, Ajith; Lees, Melissa; Holder-Espinasse, Muriel; McConnell, Vivienne; Bernhard, Birgitta; Blair, Ed; Harrison, Victoria; The DDD study; Muzny, Donna M.; Gibbs, Richard A.; Elsea, Sarah H.; Posey, Jennifer E.; Bi, Weimin; Lalani, Seema; Xia, Fan; Yang, Yaping; Eng, Christine M.; Lupski, James R.; Liu, Pengfei; Medical and Molecular Genetics, School of Medicine
    BACKGROUND: Neurodevelopmental disorders are genetically and phenotypically heterogeneous encompassing developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), structural brain abnormalities, and neurological manifestations with variants in a large number of genes (hundreds) associated. To date, a few de novo mutations potentially disrupting TCF20 function in patients with ID, ASD, and hypotonia have been reported. TCF20 encodes a transcriptional co-regulator structurally related to RAI1, the dosage-sensitive gene responsible for Smith-Magenis syndrome (deletion/haploinsufficiency) and Potocki-Lupski syndrome (duplication/triplosensitivity). METHODS: Genome-wide analyses by exome sequencing (ES) and chromosomal microarray analysis (CMA) identified individuals with heterozygous, likely damaging, loss-of-function alleles in TCF20. We implemented further molecular and clinical analyses to determine the inheritance of the pathogenic variant alleles and studied the spectrum of phenotypes. RESULTS: We report 25 unique inactivating single nucleotide variants/indels (1 missense, 1 canonical splice-site variant, 18 frameshift, and 5 nonsense) and 4 deletions of TCF20. The pathogenic variants were detected in 32 patients and 4 affected parents from 31 unrelated families. Among cases with available parental samples, the variants were de novo in 20 instances and inherited from 4 symptomatic parents in 5, including in one set of monozygotic twins. Two pathogenic loss-of-function variants were recurrent in unrelated families. Patients presented with a phenotype characterized by developmental delay, intellectual disability, hypotonia, variable dysmorphic features, movement disorders, and sleep disturbances. CONCLUSIONS: TCF20 pathogenic variants are associated with a novel syndrome manifesting clinical characteristics similar to those observed in Smith-Magenis syndrome. Together with previously described cases, the clinical entity of TCF20-associated neurodevelopmental disorders (TAND) emerges from a genotype-driven perspective.
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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