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 M, Callens T, Yunjia Chen 1, Alicia Gomes 1, Alesha D Hicks 1, Angela Sharp 1, Eric Johns 1, Kim Armfield Uhas 2, Linlea Armstrong 3, Katherine Armstrong Bosanko 4, Dusica Babovic-Vuksanovic 5, Laura Baker 6, Donald G Basel 7, Mario Bengala 8, James T Bennett 9, Chelsea Chambers 10, Lola K Clarkson 11, Maurizio Clementi 12, Fanny M Cortés 13, Mitch Cunningham 14, M Daniela D'Agostino 15, Martin B Delatycki 16, Maria C Digilio 17, Laura Dosa 18, Silvia Esposito 19, Stephanie Fox 15, Mary-Louise Freckmann 20, Christine Fauth 21, Teresa Giugliano 22, Giustini S, Allison Goetsch 24, Yael Goldberg 25, Robert S Greenwood 26, Cristin Griffis 7, Karen W Gripp 6, Punita Gupta 27, Eric Haan 28, Rachel K Hachen 29, Tamara L Haygarth 30, Concepción Hernández-Chico 31, Katelyn Hodge 32, Robert J Hopkin 33, Louanne Hudgins 34, Sandra Janssens 35, Kory Keller 36, Geraldine Kelly-Mancuso 33, Aaina Kochhar 37, Bruce R Korf 1, Andrea M Lewis 38, Jan Liebelt 39, Angie Lichty 11, Robert H Listernick 24, Michael J Lyons 11, Isabelle Maystadt 40, Mayra Martinez Ojeda 41, Carey McDougall 42, Lesley K McGregor 39, Daniela Melis 43, Nancy Mendelsohn 44, Malgorzata J M Nowaczyk 45, June Ortenberg 15, Karin Panzer 46, John G Pappas 47, Mary Ella Pierpont 48, Giulio Piluso 22, Valentina Pinna 49, Eniko K Pivnick 50, Dinel A Pond 44, Cynthia M Powell 51, Caleb Rogers 36, Noa Ruhrman Shahar 25, S Lane Rutledge 1, Veronica Saletti 19, Sarah A Sandaradura 52, Claudia Santoro 53, Ulrich A Schatz 21, Allison Schreiber 54, Daryl A Scott 38, Elizabeth A Sellars 4, Ruth Sheffer 55, Elizabeth Siqveland 44, John M Slopis 56, Rosemarie Smith 57, Alberto Spalice 58, David W Stockton 14, Haley Streff 38, Amy Theos 59, Gail E Tomlinson 60, Grace Tran 61, Pamela L Trapane 62, Eva Trevisson 12, Nicole J Ullrich 63, Jenneke Van den Ende 64, Samantha A Schrier Vergano 65, Stephanie E Wallace 9, Michael F Wangler 38, David D Weaver 32, Kaleb H Yohay 66, Elaine Zackai 42, Jonathan Zonana 36, Vickie Zurcher 54, Kathleen B M Claes 35, Marica Eoli 67, Yolanda Martin 31, Katharina Wimmer 21, Alessandro De Luca 49, Eric Legius 68, Ludwine M Messiaen 1 |
| المساهمون: | Koczkowska, M, Callens, T, Yunjia Chen, 1, Alicia Gomes, 1, Alesha, D Hicks 1, Angela Sharp, 1, Eric Johns, 1, Kim Armfield Uhas, 2, Linlea Armstrong, 3, Katherine Armstrong Bosanko, 4, Dusica Babovic-Vuksanovic, 5, Laura Baker, 6, Donald, G Basel 7, Mario Bengala, 8, James, T Bennett 9, Chelsea Chambers, 10, Lola, K Clarkson 11, Maurizio Clementi, 12, Fanny, M Cortés 13, Mitch Cunningham, 14, M Daniela D'Agostino, 15, Martin, B Delatycki 16, Maria, C Digilio 17, Laura Dosa, 18, Silvia Esposito, 19, Stephanie Fox, 15, Mary-Louise Freckmann, 20, Christine Fauth, 21, Teresa Giugliano, 22, Giustini, S, Allison Goetsch, 24, Yael Goldberg, 25, Robert, S Greenwood 26, Cristin Griffis, 7, Karen, W Gripp 6, Punita Gupta, 27, Eric Haan, 28, Rachel, K Hachen 29, Tamara, L Haygarth 30, Concepción Hernández-Chico, 31, Katelyn Hodge, 32, Robert, J Hopkin 33, Louanne Hudgins, 34, Sandra Janssens, 35, Kory Keller, 36, Geraldine Kelly-Mancuso, 33, Aaina Kochhar, 37, Bruce, R Korf 1, Andrea, M Lewis 38, Jan Liebelt, 39, Angie Lichty, 11, Robert, H Listernick 24, Michael, J Lyons 11, Isabelle Maystadt, 40, Mayra Martinez Ojeda, 41, Carey McDougall, 42, Lesley, K McGregor 39, Daniela Melis, 43, Nancy Mendelsohn, 44, Malgorzata J, M Nowaczyk 45, June Ortenberg, 15, Karin Panzer, 46, John, G Pappas 47, Mary Ella Pierpont, 48, Giulio Piluso, 22, Valentina Pinna, 49, Eniko, K Pivnick 50, Dinel, A Pond 44, Cynthia, M Powell 51, Caleb Rogers, 36, Noa Ruhrman Shahar, 25, S Lane Rutledge, 1, Veronica Saletti, 19, Sarah, A Sandaradura 52, Claudia Santoro, 53, Ulrich, A Schatz 21, Allison Schreiber, 54, Daryl, A Scott 38, Elizabeth, A Sellars 4, Ruth Sheffer, 55, Elizabeth Siqveland, 44, John, M Slopis 56, Rosemarie Smith, 57, Alberto Spalice, 58, David, W Stockton 14, Haley Streff, 38, Amy Theos, 59, Gail, E Tomlinson 60, Grace Tran, 61, Pamela, L Trapane 62, Eva Trevisson, 12, Nicole, J Ullrich 63, Jenneke Van den Ende, 64, Samantha, A Schrier Vergano 65, Stephanie, E Wallace 9, Michael, F Wangler 38, David, D Weaver 32, Kaleb, H Yohay 66, Elaine Zackai, 42, Jonathan Zonana, 36 |
| بيانات النشر: | Wiley Periodicals, Inc. |
| سنة النشر: | 2020 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| مصطلحات موضوعية: | NF1, genotype-phenotype correlation, p.Arg1276, p.Lys1423, p.Met1149 |
| 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 |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31595648; info:eu-repo/semantics/altIdentifier/wos/WOS:000492598500001; volume:41; issue:1; firstpage:299; lastpage:315; numberofpages:17; journal:HUMAN MUTATION; https://hdl.handle.net/11573/1666081Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85074609550 |
| DOI: | 10.1002/humu.23929 |
| الإتاحة: | https://doi.org/10.1002/humu.23929Test https://hdl.handle.net/11573/1666081Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.12030DF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/humu.23929 |
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