Rare mutations of FGFR2 causing apert syndrome: identification of the first partial gene deletion, and an Alu element insertion from a new subfamily.

Human Mutation
Elena G BochukovaAndrew O M Wilkie

Abstract

Apert syndrome (AS) is a severe disorder, characterized by craniosynostosis and complex syndactyly of the hands and feet. Two heterozygous gain-of-function substitutions (Ser252Trp and Pro253Arg) in exon IIIa of fibroblast growth factor receptor 2 (FGFR2) are responsible for >98% of cases. Here we describe two novel mutations in FGFR2 in the two patients in whom a mutation had not previously been found in our cohort of 227 AS cases. The first is a 1.93-kb deletion, removing exon IIIc and substantial portions of the flanking introns. This is the first large FGFR2 deletion described in any individual with craniosynostosis. The other mutation is a 5' truncated Alu insertion into exon IIIc. This is the third Alu insertion identified in AS; all have occurred within an interval of only 104 bp, representing an enrichment of over a million-fold compared to the background genomic rate. We show that the inserted Alu element belongs to a small subfamily, not previously known to be mobile, which we term Alu Yk13. Both the deletion and insertion are likely to act by a similar gain-of-function mechanism in which disruption of exon IIIc leads to illegitimate mesenchymal expression of an FGFR2 spliceform containing the alternatively spliced ex...Continue Reading

References

Jan 1, 1996·Journal of Molecular Evolution·M A BatzerE Zuckerkandl
May 1, 1996·Nature Genetics·D M MoloneyA O Wilkie
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·S C RobertsonD J Donoghue
Feb 11, 1999·American Journal of Human Genetics·M OldridgeA O Wilkie
May 20, 1999·Molecular Biology and Evolution·H J BandeltA Röhl
Jul 29, 1999·Human Mutation·M R Passos-BuenoH Kitoh
Mar 11, 2000·American Journal of Human Genetics·R L GlaserE W Jabs
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·K YuD M Ornitz
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·K Yu, D M Ornitz
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·M K HajihosseiniC Dickson
Jun 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·O A IbrahimiM Mohammadi
May 4, 2002·Nature Reviews. Genetics·Mark A Batzer, Prescott L Deininger
Aug 9, 2002·Theoretical Population Biology·Jerzy JurkaOleksiy Kokhanyy
Sep 6, 2002·Genome Research·Astrid M Roy-EngelPrescott L Deininger
Oct 3, 2002·American Journal of Medical Genetics·Andrew O M WilkieBen C J Hamel
Jun 5, 2003·Molecular Biology and Evolution·Abdel-Halim SalemMark A Batzer
Sep 15, 2004·Trends in Genetics : TIG·Richard CordauxMark A Batzer
Apr 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Anne GorielyAndrew O M Wilkie
May 3, 2005·Cytokine & Growth Factor Reviews·Moosa MohammadiOmar A Ibrahimi
Jan 18, 2006·Nucleic Acids Research·Ruben H HovhannisyanRuss P Carstens
Feb 28, 2006·Genes & Genetic Systems·Eun-Sil ParkHeui-Soo Kim
Mar 3, 2007·Trends in Genetics : TIG·Ryan E MillsScott E Devine
Sep 1, 2007·PLoS Biology·Jian QinNorman Arnheim
Feb 8, 2008·The Journal of Biological Chemistry·Puneet SethMariano A Garcia-Blanco
Oct 17, 2008·Genomic Medicine·Jian-Min ChenDavid N Cooper

❮ Previous
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Citations

Aug 9, 2012·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Greg Holmes
Jan 21, 2011·European Journal of Human Genetics : EJHG·David Johnson, Andrew O M Wilkie
Sep 29, 2011·BMC Medical Genetics·Aimee L FenwickAndrew O M Wilkie
Sep 4, 2010·Mobile DNA·Kathryn A O'Donnell, Kathleen H Burns
Feb 4, 2014·European Journal of Medical Genetics·Aimé LumakaKoenraad Devriendt
Jan 22, 2013·Gene·Kristel Kaer, Mart Speek
Jan 29, 2010·Gynecologic Oncology·Sara A ByronPamela M Pollock
May 4, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Roopa PurushothamanMichael L Cunningham
Oct 16, 2013·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·T RoscioliM F Buckley
Sep 18, 2010·Human Mutation·Philip M BoonePawel Stankiewicz
Oct 2, 2014·European Journal of Human Genetics : EJHG·Beatriz Paumard-HernándezKaren E Heath
Dec 20, 2012·Organogenesis·Kshemendra Senarath-YapaDerrick C Wan
May 10, 2016·Mobile DNA·Dustin C Hancks, Haig H Kazazian
Sep 22, 2010·The Journal of Craniofacial Surgery·Dimple Sureka, Louanne Hudgins
Feb 19, 2020·Genome Medicine·Jacob J AdashekRazelle Kurzrock
Feb 6, 2019·Biomedical Reports·Anh Lan Thi LuongHoang Ha Chu
Jul 15, 2020·ELife·Md Rakibul HasanDavid Pc Rice
Jul 6, 2016·The Journal of Craniofacial Surgery·David J DavidMark Moore
Sep 12, 2015·The Journal of Craniofacial Surgery·Irene M J Mathijssen
Dec 7, 2018·Frontiers in Genetics·Michaela ProchazkovaOphir D Klein
Dec 29, 2018·Maxillofacial Plastic and Reconstructive Surgery·Bong Kuen ChaSuk Keun Lee
Jul 18, 2009·American Journal of Medical Genetics. Part a·Anne SlavotinekMichael Friez
Oct 27, 2021·Annals of Plastic Surgery·Maxwell M WangJustine C Lee
Nov 5, 2021·BMC Genomics·Matias I AutioShyam Prabhakar

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