Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome

Journal of Medical Genetics
Guilherme Lopes YamamotoDébora Romeo Bertola

Abstract

Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes...Continue Reading

References

Apr 1, 1995·Human Molecular Genetics·H KurahashiI Nishisho
Nov 1, 1994·American Journal of Medical Genetics·I van der BurgtE Mariman
Dec 17, 2005·The Journal of Biological Chemistry·Tanju G NacakJens Kroll
Oct 6, 2006·Genetic Testing·Débora R BertolaJosé Eduardo Krieger
Jun 26, 2007·Journal of Medical Genetics·Martin ZenkerKerstin Kutsche
Oct 24, 2007·Lancet·Lisa J Kobrynski, Kathleen E Sullivan
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
May 27, 2009·Current Opinion in Genetics & Development·William E Tidyman, Katherine A Rauen
Jun 29, 2010·Genetic Testing and Molecular Biomarkers·Amanda Salem BrasilDébora Romeo Bertola
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Jul 22, 2010·Molecular Syndromology·M TartagliaB D Gelb
Sep 30, 2010·Pediatrics·Alicia A RomanoJacqueline A Noonan
Jul 27, 2011·Biochemical Pharmacology·Stéphane PierreXavier Coumoul
Dec 14, 2011·Acta Neuropathologica·Steven L Carroll
May 11, 2013·Cancer Discovery·Pablo E Hollstein, Karen Cichowski
Aug 7, 2013·Nature Genetics·Veronique FrattiniAntonio Iavarone
Jul 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Peng-Chieh ChenRaju Kucherlapati
Aug 16, 2014·American Journal of Medical Genetics. Part a·Débora R BertolaAlexandre C Pereira
Oct 23, 2014·European Journal of Human Genetics : EJHG·Irene PaganiniLaura Papi
Dec 7, 2014·Neurology·Miriam J SmithD Gareth Evans

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Citations

Sep 6, 2015·European Journal of Medical Genetics·Mylène TajanArmelle Yart
Sep 18, 2015·American Journal of Medical Genetics. Part a·Geoffrey D McWilliamsCarol Clericuzio
Jun 9, 2016·Human Genome Variation·Matthew S HestandJoris R Vermeesch
Jul 16, 2015·Human Mutation·Viviana CordedduMarco Tartaglia
Oct 9, 2015·Journal of Human Genetics·Yoko AokiYoichi Matsubara
Apr 22, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Karim KouzMartin Zenker
Jun 2, 2016·Brain and Behavior·Renée L RoelofsJos I M Egger
Jul 15, 2016·Human Molecular Genetics·William E Tidyman, Katherine A Rauen
Jan 12, 2017·PLoS Genetics·Ileena MitraLauren A Weiss
Feb 18, 2017·American Journal of Medical Genetics. Part a·Débora BertolaChong Kim
Jun 9, 2017·European Journal of Human Genetics : EJHG·Franziska AltmüllerMartin Zenker
Jun 2, 2017·Prenatal Diagnosis·Marwan M AliMary E Norton
Jul 28, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hanan E ShamseldinFowzan S Alkuraya
Jul 20, 2018·Current Opinion in Pediatrics·Mary Ella Pierpont, Maria Cristina Digilio
Sep 22, 2018·American Journal of Medical Genetics. Part a·Natario L CouserArthur S Aylsworth
Jun 21, 2018·Endocrine Reviews·Mylène TajanArmelle Yart
Feb 2, 2019·Chinese Medical Journal·Yuan DingChun-Xiu Gong
Feb 23, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jennifer J JohnstonLeslie G Biesecker
Mar 22, 2019·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Kris P T YuIvan F M Lo
Jan 19, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jennifer E PoseyUNKNOWN Centers for Mendelian Genomics
Mar 13, 2019·Clinical Genetics·Alistair T PagnamentaHelen Stewart
Jun 21, 2019·Clinical Genetics·Xin LiXiumin Wang
Aug 20, 2019·Current Opinion in Oncology·Dorothy HallidayD Gareth Evans
Feb 6, 2020·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Léa Linglart, Bruce D Gelb
Dec 13, 2016·Current Genetic Medicine Reports·William E Tidyman, Katherine A Rauen
Mar 16, 2017·JCI Insight·Erin M HigginsMichael J Ackerman
Feb 28, 2019·European Journal of Human Genetics : EJHG·Nadine N HauerChristian T Thiel

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