Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations

Human Mutation
Christèle DubourgVéronique David

Abstract

Holoprosencephaly (HPE; 1 out of 16,000 live births; 1 out of 250 conceptuses) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, affecting both the forebrain and the face. Clinical expressivity is variable, ranging from a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial dominant autosomic HPE. The disease is genetically heterogeneous, but additional environmental agents also contribute to the etiology of HPE. In our cohort of 200 patients, 34 heterozygous mutations were identified, 24 of them being novel ones: 13 out of 17 in the Sonic hedgehog gene (SHH); 4 out of 7 in ZIC2; and 7 out of 8 in SIX3. The two mutations identified in TGIF have already been reported. Novel phenotypes associated with a mutation have been described, such as abnormalities of the pituitary gland and corpus callosum, colobomatous microphthalmia, choanal aperture stenosis, and isolated cleft lip. This study confirms the great genetic heterogeneity of the disease, the important phenotypic variability in HPE families, and the difficulty to establish genotype-phenotype correlations.

References

Nov 1, 1996·Nature Genetics·E RoesslerM Muenke
Apr 1, 1996·Developmental Dynamics : an Official Publication of the American Association of Anatomists·E BertolinoR G Clerc
Apr 13, 1999·Cell·D WottonJ Massagué
Oct 21, 1999·Molecular Genetics and Metabolism·D E Wallis, M Muenke
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·T NagaiK Mikoshiba
Oct 20, 2000·European Journal of Human Genetics : EJHG·L PasquierS Odent
Aug 2, 2001·Human Genetics·J T den Dunnen, S E Antonarakis
Jan 26, 2002·Human Genetics·S PoveyH Wain
Feb 22, 2002·American Journal of Medical Genetics·Lúcia Y BrownStephen Brown
Oct 24, 2002·American Journal of Human Genetics·Jeffrey E Ming, Maximilian Muenke
Oct 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Erich RoesslerMaximilian Muenke

❮ Previous
Next ❯

Citations

Dec 17, 2010·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Jason E Cain, Norman D Rosenblum
Aug 25, 2006·Current Neurology and Neuroscience Reports·Jenny Carmichael, Christopher Woods
May 4, 2013·Journal of Genetics·Francesca LamiAntonio Percesepe
Jun 10, 2010·European Journal of Human Genetics : EJHG·Aimée D C PaulussenJos Herbergs
Jun 14, 2005·Nature Reviews. Genetics·Sandra L GilbertBruce T Lahn
Jun 30, 2009·Nature Structural & Molecular Biology·Ivan BosanacRobert A Lazarus
Sep 16, 2008·Human Molecular Genetics·Sabina DomenéBenjamin Feldman
Jan 5, 2011·Human Molecular Genetics·Valérie DupéVéronique David
Jul 8, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Stefanie WeberRuthild G Weber
Sep 18, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lisa G ShafferTamim Shaikh
Sep 6, 2007·Clinical Dysmorphology·Marie-France PortnoïMuriel Houang
Dec 1, 2007·Clinical Dysmorphology·Maria Leine Guion-AlmeidaRoseli Maria Zechi-Ceide
Sep 23, 2010·Current Opinion in Pediatrics·Emily F Kauvar, Maximilian Muenke
Jul 19, 2005·The British Journal of Ophthalmology·N K RaggeP A Farndon
Sep 24, 2011·Journal of Medical Genetics·Sandra MercierSylvie Odent
Mar 27, 2013·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Cristine SmoczerMichael Crawford
Dec 20, 2007·Diagnostic Pathology·Ada ChanFederico Gonzalez-Fernandez
Feb 6, 2007·Orphanet Journal of Rare Diseases·Christèle DubourgVéronique David
Dec 25, 2012·Disease Models & Mechanisms·Sandra MercierValérie Dupé
Dec 8, 2006·Annals of the New York Academy of Sciences·Rengasamy PadmanabhanSarabjit Singh
Aug 18, 2012·Clinical Endocrinology·Darya Gorbenko del BlancoAnita C S Hokken-Koelega
Nov 7, 2006·Gene Expression Patterns : GEP·Xin GengGuillermo Oliver
Nov 19, 2008·Research in Veterinary Science·Kimberly A GreerKeith E Murphy
Apr 26, 2014·Genetics and Molecular Biology·Clarice Pagani SavastanoIêda Maria Orioli
Aug 30, 2005·Advances in Pediatrics·Jules G Leroy, Jaime L Frías
Aug 5, 2004·The Journal of Biological Chemistry·Elisabeth TraiffortMartial Ruat
May 18, 2018·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Paul KruszkaMaximilian Muenke
Jun 23, 2007·Birth Defects Research. Part A, Clinical and Molecular Teratology·Kênia B El-JaickIêda M Orioli
Mar 29, 2014·Birth Defects Research. Part A, Clinical and Molecular Teratology·Clarice Pagani SavastanoIêda Maria Orioli
Sep 4, 2007·Obstetrics and Gynecology·Anna L DavidLyn S Chitty
Jun 6, 2006·American Journal of Medical Genetics. Part a·Giselda SantiagoAntonio Richieri-Costa
Sep 27, 2006·American Journal of Medical Genetics. Part a·Lucilene Arilho RibeiroAntonio Richieri-Costa
Nov 15, 2006·American Journal of Medical Genetics. Part a·Paul T JubinskyMary K Short
Mar 3, 2007·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Christa S Merzdorf
Aug 9, 2007·Human Mutation·Claude BendavidVéronique David
Jul 25, 2007·Birth Defects Research. Part A, Clinical and Molecular Teratology·Evyn J LoucksSara C Ahlgren

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.