Cargando…

Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1

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% confid...

Descripción completa

Detalles Bibliográficos
Autores principales: 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, Martinez Ojeda, Mayra, McDougall, Carey, McGregor, Lesley K., Melis, Daniela, Mendelsohn, Nancy, Nowaczyk, Malgorzata J.M., 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, Ruhrman Shahar, Noa, 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 B. M., Eoli, Marica, Martin, Yolanda, Wimmer, Katharina, De Luca, Alessandro, Legius, Eric, Messiaen, Ludwine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973139/
https://www.ncbi.nlm.nih.gov/pubmed/31595648
http://dx.doi.org/10.1002/humu.23929
_version_ 1783489984921075712
author 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
Martinez Ojeda, Mayra
McDougall, Carey
McGregor, Lesley K.
Melis, Daniela
Mendelsohn, Nancy
Nowaczyk, Malgorzata J.M.
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
Ruhrman Shahar, Noa
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 B. M.
Eoli, Marica
Martin, Yolanda
Wimmer, Katharina
De Luca, Alessandro
Legius, Eric
Messiaen, Ludwine M.
author_facet 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
Martinez Ojeda, Mayra
McDougall, Carey
McGregor, Lesley K.
Melis, Daniela
Mendelsohn, Nancy
Nowaczyk, Malgorzata J.M.
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
Ruhrman Shahar, Noa
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 B. M.
Eoli, Marica
Martin, Yolanda
Wimmer, Katharina
De Luca, Alessandro
Legius, Eric
Messiaen, Ludwine M.
author_sort Koczkowska, Magdalena
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6973139
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-69731392020-01-27 Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1 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 Martinez Ojeda, Mayra McDougall, Carey McGregor, Lesley K. Melis, Daniela Mendelsohn, Nancy Nowaczyk, Malgorzata J.M. 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 Ruhrman Shahar, Noa 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 B. M. Eoli, Marica Martin, Yolanda Wimmer, Katharina De Luca, Alessandro Legius, Eric Messiaen, Ludwine M. Hum Mutat Research Articles 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. John Wiley and Sons Inc. 2019-10-26 2020-01 /pmc/articles/PMC6973139/ /pubmed/31595648 http://dx.doi.org/10.1002/humu.23929 Text en © 2019 The Authors. Human Mutation Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
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
Martinez Ojeda, Mayra
McDougall, Carey
McGregor, Lesley K.
Melis, Daniela
Mendelsohn, Nancy
Nowaczyk, Malgorzata J.M.
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
Ruhrman Shahar, Noa
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 B. M.
Eoli, Marica
Martin, Yolanda
Wimmer, Katharina
De Luca, Alessandro
Legius, Eric
Messiaen, Ludwine M.
Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1
title Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1
title_full Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1
title_fullStr Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1
title_full_unstemmed Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1
title_short Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1
title_sort clinical spectrum of individuals with pathogenic nf1 missense variants affecting p.met1149, p.arg1276, and p.lys1423: genotype–phenotype study in neurofibromatosis type 1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973139/
https://www.ncbi.nlm.nih.gov/pubmed/31595648
http://dx.doi.org/10.1002/humu.23929
work_keys_str_mv AT koczkowskamagdalena clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT callenstom clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT chenyunjia clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT gomesalicia clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT hicksaleshad clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT sharpangela clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT johnseric clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT uhaskimarmfield clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT armstronglinlea clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT bosankokatherinearmstrong clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT babovicvuksanovicdusica clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT bakerlaura clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT baseldonaldg clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT bengalamario clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT bennettjamest clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT chamberschelsea clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT clarksonlolak clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT clementimaurizio clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT cortesfannym clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT cunninghammitch clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT dagostinomdaniela clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT delatyckimartinb clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT digiliomariac clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT dosalaura clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT espositosilvia clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT foxstephanie clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT freckmannmarylouise clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT fauthchristine clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT giuglianoteresa clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT giustinisandra clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT goetschallison clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT goldbergyael clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT greenwoodroberts clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT griffiscristin clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT grippkarenw clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT guptapunita clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT haaneric clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT hachenrachelk clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT haygarthtamaral clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT hernandezchicoconcepcion clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT hodgekatelyn clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT hopkinrobertj clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT hudginslouanne clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT janssenssandra clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT kellerkory clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT kellymancusogeraldine clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT kochharaaina clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT korfbrucer clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT lewisandream clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT liebeltjan clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT lichtyangie clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT listernickroberth clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT lyonsmichaelj clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT maystadtisabelle clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT martinezojedamayra clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT mcdougallcarey clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT mcgregorlesleyk clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT melisdaniela clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT mendelsohnnancy clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT nowaczykmalgorzatajm clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT ortenbergjune clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT panzerkarin clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT pappasjohng clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT pierpontmaryella clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT pilusogiulio clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT pinnavalentina clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT pivnickenikok clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT ponddinela clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT powellcynthiam clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT rogerscaleb clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT ruhrmanshaharnoa clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT rutledgeslane clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT salettiveronica clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT sandaradurasaraha clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT santoroclaudia clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT schatzulricha clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT schreiberallison clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT scottdaryla clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT sellarselizabetha clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT shefferruth clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT siqvelandelizabeth clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT slopisjohnm clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT smithrosemarie clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT spalicealberto clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT stocktondavidw clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT streffhaley clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT theosamy clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT tomlinsongaile clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT trangrace clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT trapanepamelal clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT trevissoneva clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT ullrichnicolej clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT vandenendejenneke clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT schrierverganosamanthaa clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT wallacestephaniee clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT wanglermichaelf clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT weaverdavidd clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT yohaykalebh clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT zackaielaine clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT zonanajonathan clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT zurchervickie clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT claeskathleenbm clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT eolimarica clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT martinyolanda clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT wimmerkatharina clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT delucaalessandro clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT legiuseric clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1
AT messiaenludwinem clinicalspectrumofindividualswithpathogenicnf1missensevariantsaffectingpmet1149parg1276andplys1423genotypephenotypestudyinneurofibromatosistype1