INTRODUCTION: RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies. MATERIALS AND METHODS: The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. We calculated diagnosis rate, correlated reported clinical findings with positive or negative test results, and identified final molecular diagnoses in 28/96 patients who tested negative for RASopathies. RESULTS: Twenty-four patients had pathogenic variants on the RASopathy panel, for a diagnostic yield of 19%. Reported features of pulmonic stenosis and ptosis were significantly correlated with a positive test result; no reported features were significantly correlated with a negative test result. We identified 27 different alternative diagnoses for patients originally suspected of having RASopathies. DISCUSSION: This study provides information that can assist in guiding differential diagnosis and genetic testing for patients suspected of having a RASopathy disorder.Genet Med advance online publication 20 October 2016.
INTRODUCTION: RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies. MATERIALS AND METHODS: The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. We calculated diagnosis rate, correlated reported clinical findings with positive or negative test results, and identified final molecular diagnoses in 28/96 patients who tested negative for RASopathies. RESULTS: Twenty-four patients had pathogenic variants on the RASopathy panel, for a diagnostic yield of 19%. Reported features of pulmonic stenosis and ptosis were significantly correlated with a positive test result; no reported features were significantly correlated with a negative test result. We identified 27 different alternative diagnoses for patients originally suspected of having RASopathies. DISCUSSION: This study provides information that can assist in guiding differential diagnosis and genetic testing for patients suspected of having a RASopathy disorder.Genet Med advance online publication 20 October 2016.
Authors: Alicia A Romano; Judith E Allanson; Jovanna Dahlgren; Bruce D Gelb; Bryan Hall; Mary Ella Pierpont; Amy E Roberts; Wanda Robinson; Clifford M Takemoto; Jacqueline A Noonan Journal: Pediatrics Date: 2010-09-27 Impact factor: 7.124
Authors: Sara Ekvall; Kerstin Sjörs; Anders Jonzon; Mauno Vihinen; Göran Annerén; Marie-Louise Bondeson Journal: Am J Med Genet A Date: 2013-12-19 Impact factor: 2.802
Authors: Peng-Chieh Chen; Jiani Yin; Hui-Wen Yu; Tao Yuan; Minerva Fernandez; Christina K Yung; Quang M Trinh; Vanya D Peltekova; Jeffrey G Reid; Erica Tworog-Dube; Margaret B Morgan; Donna M Muzny; Lincoln Stein; John D McPherson; Amy E Roberts; Richard A Gibbs; Benjamin G Neel; Raju Kucherlapati Journal: Proc Natl Acad Sci U S A Date: 2014-07-21 Impact factor: 11.205
Authors: Simone Martinelli; Alessandro De Luca; Emilia Stellacci; Cesare Rossi; Saula Checquolo; Francesca Lepri; Viviana Caputo; Marianna Silvano; Francesco Buscherini; Federica Consoli; Grazia Ferrara; Maria C Digilio; Maria L Cavaliere; Johanna M van Hagen; Giuseppe Zampino; Ineke van der Burgt; Giovanni B Ferrero; Laura Mazzanti; Isabella Screpanti; Helger G Yntema; Willy M Nillesen; Ravi Savarirayan; Martin Zenker; Bruno Dallapiccola; Bruce D Gelb; Marco Tartaglia Journal: Am J Hum Genet Date: 2010-07-08 Impact factor: 11.025
Authors: Karen W Gripp; Kimberly A Aldinger; James T Bennett; Laura Baker; Jessica Tusi; Nina Powell-Hamilton; Deborah Stabley; Katia Sol-Church; Andrew E Timms; William B Dobyns Journal: Am J Med Genet A Date: 2016-06-05 Impact factor: 2.802
Authors: Viviana Cordeddu; Jiani C Yin; Cecilia Gunnarsson; Carl Virtanen; Séverine Drunat; Francesca Lepri; Alessandro De Luca; Cesare Rossi; Andrea Ciolfi; Trevor J Pugh; Alessandro Bruselles; James R Priest; Len A Pennacchio; Zhibin Lu; Arnavaz Danesh; Rene Quevedo; Alaa Hamid; Simone Martinelli; Francesca Pantaleoni; Maria Gnazzo; Paola Daniele; Christina Lissewski; Gianfranco Bocchinfuso; Lorenzo Stella; Sylvie Odent; Nicole Philip; Laurence Faivre; Marketa Vlckova; Eva Seemanova; Cristina Digilio; Martin Zenker; Giuseppe Zampino; Alain Verloes; Bruno Dallapiccola; Amy E Roberts; Hélène Cavé; Bruce D Gelb; Benjamin G Neel; Marco Tartaglia Journal: Hum Mutat Date: 2015-08-03 Impact factor: 4.878
Authors: Alessandro De Luca; Irene Bottillo; Anna Sarkozy; Claudio Carta; Cinzia Neri; Emanuele Bellacchio; Annalisa Schirinzi; Emanuela Conti; Giuseppe Zampino; Agatino Battaglia; Silvia Majore; Maria M Rinaldi; Massimo Carella; Bruno Marino; Antonio Pizzuti; Maria Cristina Digilio; Marco Tartaglia; Bruno Dallapiccola Journal: Am J Hum Genet Date: 2005-10-26 Impact factor: 11.025
Authors: Sue Richards; Nazneen Aziz; Sherri Bale; David Bick; Soma Das; Julie Gastier-Foster; Wayne W Grody; Madhuri Hegde; Elaine Lyon; Elaine Spector; Karl Voelkerding; Heidi L Rehm Journal: Genet Med Date: 2015-03-05 Impact factor: 8.822
Authors: Joseph D Khoury; Eric Solary; Oussama Abla; Yassmine Akkari; Rita Alaggio; Jane F Apperley; Rafael Bejar; Emilio Berti; Lambert Busque; John K C Chan; Weina Chen; Xueyan Chen; Wee-Joo Chng; John K Choi; Isabel Colmenero; Sarah E Coupland; Nicholas C P Cross; Daphne De Jong; M Tarek Elghetany; Emiko Takahashi; Jean-Francois Emile; Judith Ferry; Linda Fogelstrand; Michaela Fontenay; Ulrich Germing; Sumeet Gujral; Torsten Haferlach; Claire Harrison; Jennelle C Hodge; Shimin Hu; Joop H Jansen; Rashmi Kanagal-Shamanna; Hagop M Kantarjian; Christian P Kratz; Xiao-Qiu Li; Megan S Lim; Keith Loeb; Sanam Loghavi; Andrea Marcogliese; Soheil Meshinchi; Phillip Michaels; Kikkeri N Naresh; Yasodha Natkunam; Reza Nejati; German Ott; Eric Padron; Keyur P Patel; Nikhil Patkar; Jennifer Picarsic; Uwe Platzbecker; Irene Roberts; Anna Schuh; William Sewell; Reiner Siebert; Prashant Tembhare; Jeffrey Tyner; Srdan Verstovsek; Wei Wang; Brent Wood; Wenbin Xiao; Cecilia Yeung; Andreas Hochhaus Journal: Leukemia Date: 2022-06-22 Impact factor: 12.883
Authors: Dena R Matalon; David A Stevenson; Elizabeth J Bhoj; Avni B Santani; Beth Keena; Meryl S Cohen; Angela E Lin; Sarah E Sheppard; Elaine H Zackai Journal: Am J Med Genet A Date: 2021-03-08 Impact factor: 2.802
Authors: Robert J Allaway; Sara J C Gosline; Salvatore La Rosa; Pamela Knight; Annette Bakker; Justin Guinney; Lu Q Le Journal: Br J Cancer Date: 2018-04-26 Impact factor: 7.640