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...
Gespeichert in:
| Veröffentlicht in: | HUMAN MUTATION 2020-01, Vol.41 (1), p.299-315 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 315 |
|---|---|
| container_issue | 1 |
| container_start_page | 299 |
| container_title | HUMAN MUTATION |
| container_volume | 41 |
| creator | 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 Cortes, 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 Hernandez-Chico, Concepcion 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 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 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 Vergano, Samantha A. Schrier Wallace, Stephanie E Wangler, Michael F Weaver, David D Yohay, Kaleb H Zackai, Elaine Zonana, Jonathan |
| 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 |
| format | Article |
| fullrecord | <record><control><sourceid>kuleuven</sourceid><recordid>TN_cdi_kuleuven_dspace_123456789_652053</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>123456789_652053</sourcerecordid><originalsourceid>FETCH-kuleuven_dspace_123456789_6520533</originalsourceid><addsrcrecordid>eNqVjj1OxDAQhVOAxPJzh-ko2KA4jpMNHVqxogAq-sjEk8SQ2FbGDuRKnBIL7QGgmjeab957J8mGZaJOq6ouzpJzovcsy3ZC8E3yvR-10a0cgRy2fg4T2A60UXrRKsiR4FP7AZz0g-0xkvByYDBpIjSEsMhZS-MJZNfFd216cLfP6Bkr6m2U93PP8qrcgjQqrk8rsSLndxCtrF8dpm44KiAf1BqTwWCYbaffZjtJb0kT_N7ZZXLaxUJ4dZwXyfXh4XX_mH6EEcOCplHkZIsNy3khympXN6XIM8H5f8ibv5GN__L8B9RAbCc</addsrcrecordid><sourcetype>Institutional Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><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><source>Lirias (KU Leuven Association)</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>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 ; Cortes, 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 ; Hernandez-Chico, Concepcion ; 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 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 ; 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 ; Vergano, Samantha A. Schrier ; Wallace, Stephanie E ; Wangler, Michael F ; Weaver, David D ; Yohay, Kaleb H ; Zackai, Elaine ; Zonana, Jonathan</creator><creatorcontrib>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 ; Cortes, 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 ; Hernandez-Chico, Concepcion ; 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 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 ; 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 ; Vergano, Samantha A. Schrier ; Wallace, Stephanie E ; Wangler, Michael F ; Weaver, David D ; Yohay, Kaleb H ; Zackai, Elaine ; Zonana, Jonathan</creatorcontrib><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.</description><identifier>ISSN: 1059-7794</identifier><language>eng</language><publisher>WILEY-HINDAWI</publisher><ispartof>HUMAN MUTATION, 2020-01, Vol.41 (1), p.299-315</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,27837</link.rule.ids></links><search><creatorcontrib>Koczkowska, Magdalena</creatorcontrib><creatorcontrib>Callens, Tom</creatorcontrib><creatorcontrib>Chen, Yunjia</creatorcontrib><creatorcontrib>Gomes, Alicia</creatorcontrib><creatorcontrib>Hicks, Alesha D</creatorcontrib><creatorcontrib>Sharp, Angela</creatorcontrib><creatorcontrib>Johns, Eric</creatorcontrib><creatorcontrib>Uhas, Kim Armfield</creatorcontrib><creatorcontrib>Armstrong, Linlea</creatorcontrib><creatorcontrib>Bosanko, Katherine Armstrong</creatorcontrib><creatorcontrib>Babovic-Vuksanovic, Dusica</creatorcontrib><creatorcontrib>Baker, Laura</creatorcontrib><creatorcontrib>Basel, Donald G</creatorcontrib><creatorcontrib>Bengala, Mario</creatorcontrib><creatorcontrib>Bennett, James T</creatorcontrib><creatorcontrib>Chambers, Chelsea</creatorcontrib><creatorcontrib>Clarkson, Lola K</creatorcontrib><creatorcontrib>Clementi, Maurizio</creatorcontrib><creatorcontrib>Cortes, Fanny M</creatorcontrib><creatorcontrib>Cunningham, Mitch</creatorcontrib><creatorcontrib>D'Agostino, M. Daniela</creatorcontrib><creatorcontrib>Delatycki, Martin B</creatorcontrib><creatorcontrib>Digilio, Maria C</creatorcontrib><creatorcontrib>Dosa, Laura</creatorcontrib><creatorcontrib>Esposito, Silvia</creatorcontrib><creatorcontrib>Fox, Stephanie</creatorcontrib><creatorcontrib>Freckmann, Mary-Louise</creatorcontrib><creatorcontrib>Fauth, Christine</creatorcontrib><creatorcontrib>Giugliano, Teresa</creatorcontrib><creatorcontrib>Giustini, Sandra</creatorcontrib><creatorcontrib>Goetsch, Allison</creatorcontrib><creatorcontrib>Goldberg, Yael</creatorcontrib><creatorcontrib>Greenwood, Robert S</creatorcontrib><creatorcontrib>Griffis, Cristin</creatorcontrib><creatorcontrib>Gripp, Karen W</creatorcontrib><creatorcontrib>Gupta, Punita</creatorcontrib><creatorcontrib>Haan, Eric</creatorcontrib><creatorcontrib>Hachen, Rachel K</creatorcontrib><creatorcontrib>Haygarth, Tamara L</creatorcontrib><creatorcontrib>Hernandez-Chico, Concepcion</creatorcontrib><creatorcontrib>Hodge, Katelyn</creatorcontrib><creatorcontrib>Hopkin, Robert J</creatorcontrib><creatorcontrib>Hudgins, Louanne</creatorcontrib><creatorcontrib>Janssens, Sandra</creatorcontrib><creatorcontrib>Keller, Kory</creatorcontrib><creatorcontrib>Kelly-Mancuso, Geraldine</creatorcontrib><creatorcontrib>Kochhar, Aaina</creatorcontrib><creatorcontrib>Korf, Bruce R</creatorcontrib><creatorcontrib>Lewis, Andrea M</creatorcontrib><creatorcontrib>Liebelt, Jan</creatorcontrib><creatorcontrib>Lichty, Angie</creatorcontrib><creatorcontrib>Listernick, Robert H</creatorcontrib><creatorcontrib>Lyons, Michael J</creatorcontrib><creatorcontrib>Maystadt, Isabelle</creatorcontrib><creatorcontrib>Ojeda, Mayra Martinez</creatorcontrib><creatorcontrib>McDougall, Carey</creatorcontrib><creatorcontrib>McGregor, Lesley K</creatorcontrib><creatorcontrib>Melis, Daniela</creatorcontrib><creatorcontrib>Mendelsohn, Nancy</creatorcontrib><creatorcontrib>Nowaczyk, Malgorzata J.M</creatorcontrib><creatorcontrib>Ortenberg, June</creatorcontrib><creatorcontrib>Panzer, Karin</creatorcontrib><creatorcontrib>Pappas, John G</creatorcontrib><creatorcontrib>Pierpont, Mary Ella</creatorcontrib><creatorcontrib>Piluso, Giulio</creatorcontrib><creatorcontrib>Pinna, Valentina</creatorcontrib><creatorcontrib>Pivnick, Eniko K</creatorcontrib><creatorcontrib>Pond, Dinel A</creatorcontrib><creatorcontrib>Powell, Cynthia M</creatorcontrib><creatorcontrib>Rogers, Caleb</creatorcontrib><creatorcontrib>Shahar, Noa Ruhrman</creatorcontrib><creatorcontrib>Rutledge, S. Lane</creatorcontrib><creatorcontrib>Saletti, Veronica</creatorcontrib><creatorcontrib>Sandaradura, Sarah A</creatorcontrib><creatorcontrib>Santoro, Claudia</creatorcontrib><creatorcontrib>Schatz, Ulrich A</creatorcontrib><creatorcontrib>Schreiber, Allison</creatorcontrib><creatorcontrib>Scott, Daryl A</creatorcontrib><creatorcontrib>Sellars, Elizabeth A</creatorcontrib><creatorcontrib>Sheffer, Ruth</creatorcontrib><creatorcontrib>Siqveland, Elizabeth</creatorcontrib><creatorcontrib>Slopis, John M</creatorcontrib><creatorcontrib>Smith, Rosemarie</creatorcontrib><creatorcontrib>Spalice, Alberto</creatorcontrib><creatorcontrib>Stockton, David W</creatorcontrib><creatorcontrib>Streff, Haley</creatorcontrib><creatorcontrib>Theos, Amy</creatorcontrib><creatorcontrib>Tomlinson, Gail E</creatorcontrib><creatorcontrib>Tran, Grace</creatorcontrib><creatorcontrib>Trapane, Pamela L</creatorcontrib><creatorcontrib>Trevisson, Eva</creatorcontrib><creatorcontrib>Ullrich, Nicole J</creatorcontrib><creatorcontrib>Van den Ende, Jenneke</creatorcontrib><creatorcontrib>Vergano, Samantha A. Schrier</creatorcontrib><creatorcontrib>Wallace, Stephanie E</creatorcontrib><creatorcontrib>Wangler, Michael F</creatorcontrib><creatorcontrib>Weaver, David D</creatorcontrib><creatorcontrib>Yohay, Kaleb H</creatorcontrib><creatorcontrib>Zackai, Elaine</creatorcontrib><creatorcontrib>Zonana, Jonathan</creatorcontrib><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><title>HUMAN MUTATION</title><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.</description><issn>1059-7794</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqVjj1OxDAQhVOAxPJzh-ko2KA4jpMNHVqxogAq-sjEk8SQ2FbGDuRKnBIL7QGgmjeab957J8mGZaJOq6ouzpJzovcsy3ZC8E3yvR-10a0cgRy2fg4T2A60UXrRKsiR4FP7AZz0g-0xkvByYDBpIjSEsMhZS-MJZNfFd216cLfP6Bkr6m2U93PP8qrcgjQqrk8rsSLndxCtrF8dpm44KiAf1BqTwWCYbaffZjtJb0kT_N7ZZXLaxUJ4dZwXyfXh4XX_mH6EEcOCplHkZIsNy3khympXN6XIM8H5f8ibv5GN__L8B9RAbCc</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Koczkowska, Magdalena</creator><creator>Callens, Tom</creator><creator>Chen, Yunjia</creator><creator>Gomes, Alicia</creator><creator>Hicks, Alesha D</creator><creator>Sharp, Angela</creator><creator>Johns, Eric</creator><creator>Uhas, Kim Armfield</creator><creator>Armstrong, Linlea</creator><creator>Bosanko, Katherine Armstrong</creator><creator>Babovic-Vuksanovic, Dusica</creator><creator>Baker, Laura</creator><creator>Basel, Donald G</creator><creator>Bengala, Mario</creator><creator>Bennett, James T</creator><creator>Chambers, Chelsea</creator><creator>Clarkson, Lola K</creator><creator>Clementi, Maurizio</creator><creator>Cortes, Fanny M</creator><creator>Cunningham, Mitch</creator><creator>D'Agostino, M. Daniela</creator><creator>Delatycki, Martin B</creator><creator>Digilio, Maria C</creator><creator>Dosa, Laura</creator><creator>Esposito, Silvia</creator><creator>Fox, Stephanie</creator><creator>Freckmann, Mary-Louise</creator><creator>Fauth, Christine</creator><creator>Giugliano, Teresa</creator><creator>Giustini, Sandra</creator><creator>Goetsch, Allison</creator><creator>Goldberg, Yael</creator><creator>Greenwood, Robert S</creator><creator>Griffis, Cristin</creator><creator>Gripp, Karen W</creator><creator>Gupta, Punita</creator><creator>Haan, Eric</creator><creator>Hachen, Rachel K</creator><creator>Haygarth, Tamara L</creator><creator>Hernandez-Chico, Concepcion</creator><creator>Hodge, Katelyn</creator><creator>Hopkin, Robert J</creator><creator>Hudgins, Louanne</creator><creator>Janssens, Sandra</creator><creator>Keller, Kory</creator><creator>Kelly-Mancuso, Geraldine</creator><creator>Kochhar, Aaina</creator><creator>Korf, Bruce R</creator><creator>Lewis, Andrea M</creator><creator>Liebelt, Jan</creator><creator>Lichty, Angie</creator><creator>Listernick, Robert H</creator><creator>Lyons, Michael J</creator><creator>Maystadt, Isabelle</creator><creator>Ojeda, Mayra Martinez</creator><creator>McDougall, Carey</creator><creator>McGregor, Lesley K</creator><creator>Melis, Daniela</creator><creator>Mendelsohn, Nancy</creator><creator>Nowaczyk, Malgorzata J.M</creator><creator>Ortenberg, June</creator><creator>Panzer, Karin</creator><creator>Pappas, John G</creator><creator>Pierpont, Mary Ella</creator><creator>Piluso, Giulio</creator><creator>Pinna, Valentina</creator><creator>Pivnick, Eniko K</creator><creator>Pond, Dinel A</creator><creator>Powell, Cynthia M</creator><creator>Rogers, Caleb</creator><creator>Shahar, Noa Ruhrman</creator><creator>Rutledge, S. Lane</creator><creator>Saletti, Veronica</creator><creator>Sandaradura, Sarah A</creator><creator>Santoro, Claudia</creator><creator>Schatz, Ulrich A</creator><creator>Schreiber, Allison</creator><creator>Scott, Daryl A</creator><creator>Sellars, Elizabeth A</creator><creator>Sheffer, Ruth</creator><creator>Siqveland, Elizabeth</creator><creator>Slopis, John M</creator><creator>Smith, Rosemarie</creator><creator>Spalice, Alberto</creator><creator>Stockton, David W</creator><creator>Streff, Haley</creator><creator>Theos, Amy</creator><creator>Tomlinson, Gail E</creator><creator>Tran, Grace</creator><creator>Trapane, Pamela L</creator><creator>Trevisson, Eva</creator><creator>Ullrich, Nicole J</creator><creator>Van den Ende, Jenneke</creator><creator>Vergano, Samantha A. Schrier</creator><creator>Wallace, Stephanie E</creator><creator>Wangler, Michael F</creator><creator>Weaver, David D</creator><creator>Yohay, Kaleb H</creator><creator>Zackai, Elaine</creator><creator>Zonana, Jonathan</creator><general>WILEY-HINDAWI</general><scope>FZOIL</scope></search><sort><creationdate>202001</creationdate><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><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 ; Cortes, 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 ; Hernandez-Chico, Concepcion ; 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 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 ; 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 ; Vergano, Samantha A. Schrier ; Wallace, Stephanie E ; Wangler, Michael F ; Weaver, David D ; Yohay, Kaleb H ; Zackai, Elaine ; Zonana, Jonathan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-kuleuven_dspace_123456789_6520533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koczkowska, Magdalena</creatorcontrib><creatorcontrib>Callens, Tom</creatorcontrib><creatorcontrib>Chen, Yunjia</creatorcontrib><creatorcontrib>Gomes, Alicia</creatorcontrib><creatorcontrib>Hicks, Alesha D</creatorcontrib><creatorcontrib>Sharp, Angela</creatorcontrib><creatorcontrib>Johns, Eric</creatorcontrib><creatorcontrib>Uhas, Kim Armfield</creatorcontrib><creatorcontrib>Armstrong, Linlea</creatorcontrib><creatorcontrib>Bosanko, Katherine Armstrong</creatorcontrib><creatorcontrib>Babovic-Vuksanovic, Dusica</creatorcontrib><creatorcontrib>Baker, Laura</creatorcontrib><creatorcontrib>Basel, Donald G</creatorcontrib><creatorcontrib>Bengala, Mario</creatorcontrib><creatorcontrib>Bennett, James T</creatorcontrib><creatorcontrib>Chambers, Chelsea</creatorcontrib><creatorcontrib>Clarkson, Lola K</creatorcontrib><creatorcontrib>Clementi, Maurizio</creatorcontrib><creatorcontrib>Cortes, Fanny M</creatorcontrib><creatorcontrib>Cunningham, Mitch</creatorcontrib><creatorcontrib>D'Agostino, M. Daniela</creatorcontrib><creatorcontrib>Delatycki, Martin B</creatorcontrib><creatorcontrib>Digilio, Maria C</creatorcontrib><creatorcontrib>Dosa, Laura</creatorcontrib><creatorcontrib>Esposito, Silvia</creatorcontrib><creatorcontrib>Fox, Stephanie</creatorcontrib><creatorcontrib>Freckmann, Mary-Louise</creatorcontrib><creatorcontrib>Fauth, Christine</creatorcontrib><creatorcontrib>Giugliano, Teresa</creatorcontrib><creatorcontrib>Giustini, Sandra</creatorcontrib><creatorcontrib>Goetsch, Allison</creatorcontrib><creatorcontrib>Goldberg, Yael</creatorcontrib><creatorcontrib>Greenwood, Robert S</creatorcontrib><creatorcontrib>Griffis, Cristin</creatorcontrib><creatorcontrib>Gripp, Karen W</creatorcontrib><creatorcontrib>Gupta, Punita</creatorcontrib><creatorcontrib>Haan, Eric</creatorcontrib><creatorcontrib>Hachen, Rachel K</creatorcontrib><creatorcontrib>Haygarth, Tamara L</creatorcontrib><creatorcontrib>Hernandez-Chico, Concepcion</creatorcontrib><creatorcontrib>Hodge, Katelyn</creatorcontrib><creatorcontrib>Hopkin, Robert J</creatorcontrib><creatorcontrib>Hudgins, Louanne</creatorcontrib><creatorcontrib>Janssens, Sandra</creatorcontrib><creatorcontrib>Keller, Kory</creatorcontrib><creatorcontrib>Kelly-Mancuso, Geraldine</creatorcontrib><creatorcontrib>Kochhar, Aaina</creatorcontrib><creatorcontrib>Korf, Bruce R</creatorcontrib><creatorcontrib>Lewis, Andrea M</creatorcontrib><creatorcontrib>Liebelt, Jan</creatorcontrib><creatorcontrib>Lichty, Angie</creatorcontrib><creatorcontrib>Listernick, Robert H</creatorcontrib><creatorcontrib>Lyons, Michael J</creatorcontrib><creatorcontrib>Maystadt, Isabelle</creatorcontrib><creatorcontrib>Ojeda, Mayra Martinez</creatorcontrib><creatorcontrib>McDougall, Carey</creatorcontrib><creatorcontrib>McGregor, Lesley K</creatorcontrib><creatorcontrib>Melis, Daniela</creatorcontrib><creatorcontrib>Mendelsohn, Nancy</creatorcontrib><creatorcontrib>Nowaczyk, Malgorzata J.M</creatorcontrib><creatorcontrib>Ortenberg, June</creatorcontrib><creatorcontrib>Panzer, Karin</creatorcontrib><creatorcontrib>Pappas, John G</creatorcontrib><creatorcontrib>Pierpont, Mary Ella</creatorcontrib><creatorcontrib>Piluso, Giulio</creatorcontrib><creatorcontrib>Pinna, Valentina</creatorcontrib><creatorcontrib>Pivnick, Eniko K</creatorcontrib><creatorcontrib>Pond, Dinel A</creatorcontrib><creatorcontrib>Powell, Cynthia M</creatorcontrib><creatorcontrib>Rogers, Caleb</creatorcontrib><creatorcontrib>Shahar, Noa Ruhrman</creatorcontrib><creatorcontrib>Rutledge, S. Lane</creatorcontrib><creatorcontrib>Saletti, Veronica</creatorcontrib><creatorcontrib>Sandaradura, Sarah A</creatorcontrib><creatorcontrib>Santoro, Claudia</creatorcontrib><creatorcontrib>Schatz, Ulrich A</creatorcontrib><creatorcontrib>Schreiber, Allison</creatorcontrib><creatorcontrib>Scott, Daryl A</creatorcontrib><creatorcontrib>Sellars, Elizabeth A</creatorcontrib><creatorcontrib>Sheffer, Ruth</creatorcontrib><creatorcontrib>Siqveland, Elizabeth</creatorcontrib><creatorcontrib>Slopis, John M</creatorcontrib><creatorcontrib>Smith, Rosemarie</creatorcontrib><creatorcontrib>Spalice, Alberto</creatorcontrib><creatorcontrib>Stockton, David W</creatorcontrib><creatorcontrib>Streff, Haley</creatorcontrib><creatorcontrib>Theos, Amy</creatorcontrib><creatorcontrib>Tomlinson, Gail E</creatorcontrib><creatorcontrib>Tran, Grace</creatorcontrib><creatorcontrib>Trapane, Pamela L</creatorcontrib><creatorcontrib>Trevisson, Eva</creatorcontrib><creatorcontrib>Ullrich, Nicole J</creatorcontrib><creatorcontrib>Van den Ende, Jenneke</creatorcontrib><creatorcontrib>Vergano, Samantha A. Schrier</creatorcontrib><creatorcontrib>Wallace, Stephanie E</creatorcontrib><creatorcontrib>Wangler, Michael F</creatorcontrib><creatorcontrib>Weaver, David D</creatorcontrib><creatorcontrib>Yohay, Kaleb H</creatorcontrib><creatorcontrib>Zackai, Elaine</creatorcontrib><creatorcontrib>Zonana, Jonathan</creatorcontrib><collection>Lirias (KU Leuven Association)</collection><jtitle>HUMAN MUTATION</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koczkowska, Magdalena</au><au>Callens, Tom</au><au>Chen, Yunjia</au><au>Gomes, Alicia</au><au>Hicks, Alesha D</au><au>Sharp, Angela</au><au>Johns, Eric</au><au>Uhas, Kim Armfield</au><au>Armstrong, Linlea</au><au>Bosanko, Katherine Armstrong</au><au>Babovic-Vuksanovic, Dusica</au><au>Baker, Laura</au><au>Basel, Donald G</au><au>Bengala, Mario</au><au>Bennett, James T</au><au>Chambers, Chelsea</au><au>Clarkson, Lola K</au><au>Clementi, Maurizio</au><au>Cortes, Fanny M</au><au>Cunningham, Mitch</au><au>D'Agostino, M. Daniela</au><au>Delatycki, Martin B</au><au>Digilio, Maria C</au><au>Dosa, Laura</au><au>Esposito, Silvia</au><au>Fox, Stephanie</au><au>Freckmann, Mary-Louise</au><au>Fauth, Christine</au><au>Giugliano, Teresa</au><au>Giustini, Sandra</au><au>Goetsch, Allison</au><au>Goldberg, Yael</au><au>Greenwood, Robert S</au><au>Griffis, Cristin</au><au>Gripp, Karen W</au><au>Gupta, Punita</au><au>Haan, Eric</au><au>Hachen, Rachel K</au><au>Haygarth, Tamara L</au><au>Hernandez-Chico, Concepcion</au><au>Hodge, Katelyn</au><au>Hopkin, Robert J</au><au>Hudgins, Louanne</au><au>Janssens, Sandra</au><au>Keller, Kory</au><au>Kelly-Mancuso, Geraldine</au><au>Kochhar, Aaina</au><au>Korf, Bruce R</au><au>Lewis, Andrea M</au><au>Liebelt, Jan</au><au>Lichty, Angie</au><au>Listernick, Robert H</au><au>Lyons, Michael J</au><au>Maystadt, Isabelle</au><au>Ojeda, Mayra Martinez</au><au>McDougall, Carey</au><au>McGregor, Lesley K</au><au>Melis, Daniela</au><au>Mendelsohn, Nancy</au><au>Nowaczyk, Malgorzata J.M</au><au>Ortenberg, June</au><au>Panzer, Karin</au><au>Pappas, John G</au><au>Pierpont, Mary Ella</au><au>Piluso, Giulio</au><au>Pinna, Valentina</au><au>Pivnick, Eniko K</au><au>Pond, Dinel A</au><au>Powell, Cynthia M</au><au>Rogers, Caleb</au><au>Shahar, Noa Ruhrman</au><au>Rutledge, S. Lane</au><au>Saletti, Veronica</au><au>Sandaradura, Sarah A</au><au>Santoro, Claudia</au><au>Schatz, Ulrich A</au><au>Schreiber, Allison</au><au>Scott, Daryl A</au><au>Sellars, Elizabeth A</au><au>Sheffer, Ruth</au><au>Siqveland, Elizabeth</au><au>Slopis, John M</au><au>Smith, Rosemarie</au><au>Spalice, Alberto</au><au>Stockton, David W</au><au>Streff, Haley</au><au>Theos, Amy</au><au>Tomlinson, Gail E</au><au>Tran, Grace</au><au>Trapane, Pamela L</au><au>Trevisson, Eva</au><au>Ullrich, Nicole J</au><au>Van den Ende, Jenneke</au><au>Vergano, Samantha A. Schrier</au><au>Wallace, Stephanie E</au><au>Wangler, Michael F</au><au>Weaver, David D</au><au>Yohay, Kaleb H</au><au>Zackai, Elaine</au><au>Zonana, Jonathan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1</atitle><jtitle>HUMAN MUTATION</jtitle><date>2020-01</date><risdate>2020</risdate><volume>41</volume><issue>1</issue><spage>299</spage><epage>315</epage><pages>299-315</pages><issn>1059-7794</issn><abstract>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.</abstract><pub>WILEY-HINDAWI</pub><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1059-7794 |
| ispartof | HUMAN MUTATION, 2020-01, Vol.41 (1), p.299-315 |
| issn | 1059-7794 |
| language | eng |
| recordid | cdi_kuleuven_dspace_123456789_652053 |
| source | Lirias (KU Leuven Association); Wiley Online Library Journals Frontfile Complete |
| 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T11%3A24%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-kuleuven&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clinical%20spectrum%20of%20individuals%20with%20pathogenic%20NF1%20missense%20variants%20affecting%20p.Met1149,%20p.Arg1276,%20and%20p.Lys1423:%20genotype-phenotype%20study%20in%20neurofibromatosis%20type%201&rft.jtitle=HUMAN%20MUTATION&rft.au=Koczkowska,%20Magdalena&rft.date=2020-01&rft.volume=41&rft.issue=1&rft.spage=299&rft.epage=315&rft.pages=299-315&rft.issn=1059-7794&rft_id=info:doi/&rft_dat=%3Ckuleuven%3E123456789_652053%3C/kuleuven%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |