دورية أكاديمية
Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423 : genotype-phenotype study in neurofibromatosis type 1
| العنوان: | Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423 : genotype-phenotype study in neurofibromatosis type 1 |
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| المؤلفون: | Koczkowska, Magdalena, Callens, Tom, Chen, Yunjia, Gomes, Alicia, Hicks, Alesha D., Sharp, Angela, Johns, Eric, Uhas, Kim Armfield, Armstrong, Linlea, Bosanko, Katherine Armstrong, Babovic‐Vuksanovic, Dusica, Baker, Laura, Basel, Donald G, Bengala, Mario, Bennett, James T, Chambers, Chelsea, Clarkson, Lola K, Clementi, Maurizio, Cortés, Fanny M, Cunningham, Mitch, D'Agostino, M Daniela, Delatycki, Martin B, Digilio, Maria C, Dosa, Laura, Esposito, Silvia, Fox, Stephanie, Freckmann, Mary‐Louise, Fauth, Christine, Giugliano, Teresa, Giustini, Sandra, Goetsch, Allison, Goldberg, Yael, Greenwood, Robert S, Griffis, Cristin, Gripp, Karen W, Gupta, Punita, Haan, Eric, Hachen, Rachel K, Haygarth, Tamara L, Hernández‐Chico, Concepción, Hodge, Katelyn, Hopkin, Robert J, Hudgins, Louanne, Janssens, Sandra, Keller, Kory, Kelly‐Mancuso, Geraldine, Kochhar, Aaina, Korf, Bruce R, Lewis, Andrea M, Liebelt, Jan, Lichty, Angie, Listernick, Robert H, Lyons, Michael J, Maystadt, Isabelle, Ojeda, Mayra Martinez, McDougall, Carey, McGregor, Lesley K., Melis, Daniela, Mendelsohn, Nancy, Nowaczyk, Malgorzata JM, Ortenberg, June, Panzer, Karin, Pappas, John G, Pierpont, Mary Ella, Piluso, Giulio, Pinna, Valentina, Pivnick, Eniko K, Pond, Dinel A, Powell, Cynthia M, Rogers, Caleb, Shahar, Noa Ruhrman, Rutledge, S Lane, Saletti, Veronica, Sandaradura, Sarah A, Santoro, Claudia, Schatz, Ulrich A, Schreiber, Allison, Scott, Daryl A, Sellars, Elizabeth A, Sheffer, Ruth, Siqveland, Elizabeth, Slopis, John M, Smith, Rosemarie, Spalice, Alberto, Stockton, David W, Streff, Haley, Theos, Amy, Tomlinson, Gail E, Tran, Grace, Trapane, Pamela L, Trevisson, Eva, Ullrich, Nicole J, Van den Ende, Jenneke, Schrier Vergano, Samantha A, Wallace, Stephanie E, Wangler, Michael F, Weaver, David D, Yohay, Kaleb H, Zackai, Elaine, Zonana, Jonathan, Zurcher, Vickie, Claes, Kathleen, Eoli, Marica, Martin, Yolanda, Wimmer, Katharina, De Luca, Alessandro, Legius, Eric, Messiaen, Ludwine M |
| المصدر: | HUMAN MUTATION ; ISSN: 1059-7794 ; ISSN: 1098-1004 |
| سنة النشر: | 2020 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, genotype-phenotype correlation, NF1, p.Arg1276, p.Lys1423, p.Met1149, OPTIC PATHWAY TUMORS, SOUTH EAST WALES, AU-LAIT SPOTS, NOONAN-SYNDROME, VONRECKLINGHAUSEN NEUROFIBROMATOSIS, SPINAL NEUROFIBROMATOSIS, PULMONARY STENOSIS, NATURAL-HISTORY, INDEPENDENT NF1, MUTATIONS |
| الوصف: | We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating NF1 hotspots in the University of Alabama at Birmingham (UAB) cohort, together identified in 1.8% of unrelated NF1 individuals. About 25% (95% confidence interval: 20.5-31.2%) of individuals heterozygous for a pathogenic NF1 p.Met1149, p.Arg1276, or p.Lys1423 missense variant had a Noonan-like phenotype, which is significantly more compared with the "classic" NF1-affected cohorts (all p < .0001). Furthermore, p.Arg1276 and p.Lys1423 pathogenic missense variants were associated with a high prevalence of cardiovascular abnormalities, including pulmonic stenosis (all p < .0001), while p.Arg1276 variants had a high prevalence of symptomatic spinal neurofibromas (p < .0001) compared with "classic" NF1-affected cohorts. However, p.Met1149-positive individuals had a mild phenotype, characterized mainly by pigmentary manifestations without externally visible plexiform neurofibromas, symptomatic spinal neurofibromas or symptomatic optic pathway gliomas. As up to 0.4% of unrelated individuals in the UAB cohort carries a p.Met1149 missense variant, this finding will contribute to more accurate stratification of a significant number of NF1 individuals. Although clinically relevant genotype-phenotype correlations are rare in NF1, each affecting only a small percentage of individuals, together they impact counseling and management of a significant number of the NF1 population. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/8632274Test; http://hdl.handle.net/1854/LU-8632274Test; http://dx.doi.org/10.1002/humu.23929Test; https://biblio.ugent.be/publication/8632274/file/8639135Test |
| DOI: | 10.1002/humu.23929 |
| الإتاحة: | https://doi.org/10.1002/humu.23929Test https://biblio.ugent.be/publication/8632274Test http://hdl.handle.net/1854/LU-8632274Test https://biblio.ugent.be/publication/8632274/file/8639135Test |
| حقوق: | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND 4.0) ; info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.13D1C9B1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/humu.23929 |
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