Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles Syndrome caused by a single FLNA mutation with combined gain-of-function and loss-of-function effects

Journal of Medical Genetics
Elena ParriniR Guerrini

Abstract

Loss-of-function mutations of the FLNA gene cause a neuronal migration disorder defined as X-linked periventricular nodular heterotopia (PNH); gain-of-function mutations are associated with a group of X-linked skeletal dysplasias designed as otopalatodigital (OPD) spectrum. We describe a family in which a woman and her three daughters exhibited a complex phenotype combining PNH, epilepsy and Melnick-Needles syndrome (MNS), a skeletal disorder assigned to the OPD spectrum. All four individuals harboured a novel non-conservative missense mutation in FLNA exon 3. In all affected family members, we performed mutation analysis of the FLNA gene, RT-PCR, ultradeep sequencing analysis in FLNA cDNAs and western blot in lymphocyte cells to further characterise the mutation. We also assessed the effects on RT-PCR products of treatment of patients' lymphocytes with cycloheximide, a nonsense mediated mRNA decay (NMD) inhibitor. We identified a novel c.622G>C change in FLNA exon 3, leading to the substitution of a highly conserved aminoacid (p.Gly208Arg). Gel electrophoresis and ultradeep sequencing revealed the missense mutation as well as retention of intron 3. Cycloheximide treatment demonstrated that the aberrant mRNA transcript-retainin...Continue Reading

References

Mar 17, 2001·Nature Reviews. Molecular Cell Biology·T P StosselS S Shapiro
Mar 4, 2003·Nature Genetics·Stephen P RobertsonUNKNOWN OPD-spectrum Disorders Clinical Collaborative Group
May 4, 2004·Annals of Neurology·Fusako UsukiShigeo Ohno
Jul 31, 2004·Nature Genetics·Jill A HolbrookAndreas E Kulozik
Nov 2, 2004·Nature Cell Biology·Yuanyi Feng, Christopher A Walsh
Oct 4, 2005·Journal of Medical Genetics·D Baralle, M Baralle
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·M L GardelD A Weitz
May 11, 2006·Brain : a Journal of Neurology·E ParriniR Guerrini
Jul 17, 2007·American Journal of Medical Genetics. Part a·Sheila UngerDeborah J Morris-Rosendahl
May 1, 2008·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Pao-Lin KuoYen-Ni Teng
Feb 27, 2010·American Journal of Medical Genetics. Part a·Helena H SantosMarcos J B Aguiar
Jul 6, 2010·American Journal of Human Genetics·Yu SunMartijn H Breuning
Aug 24, 2010·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Marie Claire Y de WitGrazia M S Mancini
Jan 5, 2011·European Journal of Medical Genetics·M C Y de WitG M S Mancini
Apr 13, 2011·American Journal of Medical Genetics. Part a·Elena ParriniRenzo Guerrini
Mar 20, 2012·Brain : a Journal of Neurology·A James BarkovichWilliam B Dobyns
Jul 23, 2013·American Journal of Medical Genetics. Part a·Renske OegemaAlice S Brooks
Jun 17, 2014·Lancet Neurology·Renzo Guerrini, William B Dobyns
Aug 21, 2014·The New England Journal of Medicine·Saumya S JamuarChristopher A Walsh
Nov 20, 2014·The New England Journal of Medicine·Saumya S Jamuar, Christopher A Walsh

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Citations

Sep 26, 2015·Clinical Genetics·S NaudionP Fergelot
Oct 16, 2016·American Journal of Medical Genetics. Part a·Marco RitelliMarco Castori
Mar 27, 2018·American Journal of Medical Genetics. Part a·Careni SpencerStephen P Robertson
Dec 22, 2017·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·S StoeckleinD Prayer
Feb 29, 2020·Human Mutation·Emma M WadeStephen P Robertson
Aug 2, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Shuzhang LiangRuilin Zhang

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