Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly

Human Genetics

Volumn 127, Issue 5, 2010, Pages 555-561

  Hehr, Ute ^a,b   Pineda Alvarez, Daniel E ^c   Uyanik, Goekhan ^b   Hu, Ping ^c   Zhou, Nan ^c   Hehr, Andreas ^a   Schell Apacik, Chayim ^d,e   Altus, Carola ^f   Daumer Haas, Cornelia ^g   Meiner, Annechristin ^h   Steuernagel, Peter ⁱ   Roessler, Erich ^c   Winkler, Juergen ^j   Muenke, Maximilian ^c  

^a UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^b UNIVERSITY OF REGENSBURG   (Germany)

^c NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^d UNIVERSITY OF MUNICH   (Germany)

^e Practice for Human Genetics   (Germany)

^f Private Practice for Human Genetics   (Germany)

^g Prenatal Medicine Munich   (Germany)

^h Private Practice for Human Genetics   (Germany)

ⁱ KLINIKUM OLDENBURG   (Germany)

^j UNIVERSITY HOSPITAL ERLANGEN   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR EMX2; TRANSCRIPTION FACTOR SIX3; EYE PROTEIN; HOMEODOMAIN PROTEIN; NERVE PROTEIN; SHH PROTEIN, HUMAN; SINE OCULIS HOMEOBOX HOMOLOG 3 PROTEIN;

APLASIA; ARTICLE; BRAIN MALFORMATION; CELL MIGRATION; CHILD; FETUS; FOREBRAIN; HETEROZYGOSITY; HOLOPROSENCEPHALY; HUMAN; HYPOPLASIA; MAJOR CLINICAL STUDY; MALE; MICROGYRIA; MISSENSE MUTATION; NERVE CELL; NUCLEOTIDE SEQUENCE; OPTIC NERVE; PHENOTYPE; PRESCHOOL CHILD; PRIORITY JOURNAL; SCHIZENCEPHALY; SEPTUM PELLUCIDUM; CORTICAL DYSPLASIA; FEMALE; GENETICS; HETEROZYGOTE; MOLECULAR GENETICS; MUTATION;

BASE SEQUENCE; CHILD; CHILD, PRESCHOOL; EYE PROTEINS; FEMALE; HEDGEHOG PROTEINS; HETEROZYGOTE; HOLOPROSENCEPHALY; HOMEODOMAIN PROTEINS; HUMANS; MALE; MALFORMATIONS OF CORTICAL DEVELOPMENT; MOLECULAR SEQUENCE DATA; MUTATION; NERVE TISSUE PROTEINS;

EID: 77951632193     PISSN: 03406717     EISSN: 14321203     Source Type: Journal    
DOI: 10.1007/s00439-010-0797-4     Document Type: Article

References (30)

1. Barkovich AJ (1995) Pediatric neuroimaging. Raven Press, New York
2. AJ Barkovich D Quint 1993 Middle interhemispheric fusion: an unusual variant of holoprosencephaly Am J Neuroradiol 14 431 440 8456724 1:STN:280:DyaK3s3gs1yhsw%3D%3D (Pubitemid 23130145)
3. AJ Barkovich EM Simon NJ Clegg SL Kinsman JS Hahn 2002 Analysis of the cerebral cortex in holoprosencephaly with attention to the sylvian fissures Am J Neuroradiol 23 143 150 11827887
4. LY Brown SE Hodge WG Johnson SG Guy JS Nye S Brown 2002 Possible association of NTDs with a polyhistidine tract polymorphism in the ZIC2 gene Am J Med Genet 108 128 131 10.1002/ajmg.10221 11857562 (Pubitemid 34174316)
5. S Brunelli A Faiella V Capra V Nigro A Simeone A Cama E Boncinelli 1996 Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly Nat Genet 12 94 96 10.1038/ng0196-94 8528262 1:CAS:528: DyaK28XhsV2gsg%3D%3D (Pubitemid 26011327)
6. CJ Curry EJ Lammer V Nelson GM Shaw 2005 Schizencephaly: heterogeneous etiologies in a population of 4 million California births Am J Med Genet 137A 181 189 10.1002/ajmg.a.30862 (Pubitemid 41262686)
7. F Del Bene K Tessmar-Raible J Wittbrodt 2004 Direct interaction of geminin and Six3 in eye development Nature 427 745 749 10.1038/nature02292 14973488 1:CAS:528:DC%2BD2cXhtlajsr4%3D (Pubitemid 38294594)
8. S Domené E Roessler KB El-Jaick M Snir JL Brown JI Vélez S Bale F Lacbawan M Muenke B Feldman 2008 Mutations in the human SIX3 gene in holoprosencephaly are loss of function Hum Mol Genet 17 3919 3928 10.1093/hmg/ddn294 18791198 1:CAS:528:DC%2BD1cXhsVeqsr7I (Pubitemid 352762854)
9. C Dubourg C Bendavid L Pasquier C Henry S Odent V David 2007 Holoprosencephaly Orphanet J Rare Dis 2 8 21 10.1186/1750-1172-2-8 17274816
10. A Faiella S Brunelli T Granata L D'Incerti R Cardini C Lenti G Battaglia E Boncinelli 1997 A number of schizencephaly patients including 2 brothers are heterozygous for germline mutations in the homeobox gene EMX2 Eur J Hum Genet 5 186 190 9359037 1:CAS:528:DyaK2sXnt1Omtr0%3D (Pubitemid 27453897)
11. X Geng C Speirs O Lagutin A Inbal W Liu L Solnica-Krezel Y Jeong DJ Epstein G Oliver 2008 Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly Dev Cell 15 236 247 10.1016/j.devcel.2008.07.003 18694563 1:CAS:528: DC%2BD1cXhtVehtL%2FP
12. R Guerrini T Filippi 2005 Neuronal migration disorders, genetics, and epileptogenesis J Child Neurol 20 287 299 10.1177/08830738050200040401 15921228 (Pubitemid 40766985)
13. N Hayashi Y Tsutsumi AJ Barkovich 2002 Morphological features and associated anomalies of schizencephaly in the clinical population: detailed analysis of MR images Neuroradiology 44 418 427 10.1007/s00234-001-0719-1 12012128 1:STN:280:DC%2BD383nt1Cntw%3D%3D (Pubitemid 36097194)
14. U Hehr C Gross U Diebold D Wahl U Beudt P Heidemann A Hehr D Mueller 2004 Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation Eur J Pediatr 163 347 352 10.1007/s00431-004-1459-0 15107988 (Pubitemid 38916367)
15. AC Hilburger JK Willis E Bouldin A Henderson-Tilton 1993 Familial schizencephaly Brain Dev 15 234 236 10.1016/0387-7604(93)90072-G 8214352 1:STN:280:DyaK2c%2FislKktA%3D%3D (Pubitemid 23198745)
16. P Iannetti G Nigro A Spalice A Faiella E Boncinelli 1998 Cytomegalovirus infection and schizencephaly: case reports Ann Neurol 43 123 127 10.1002/ana.410430122 9450779 1:STN:280:DyaK1c7htFamtw%3D%3D (Pubitemid 28124659)
17. F Lacbawan BD Solomon E Roessler K El-Jaick S Domené JI Vélez N Zhou D Hadley JZ Balog R Long A Fryer W Smith S Omar SD McLean K Clarkson A Lichty NJ Clegg MR Delgado E Levey E Stashinko L Potocki MI Vanallen J Clayton-Smith D Donnai DW Bianchi PB Juliusson PR Njølstad HG Brunner JC Carey U Hehr J Müsebeck PF Wieacker A Postra RC Hennekam MJ van den Boogaard A van Haeringen A Paulussen J Herbergs CT Schrander-Stumpel AR Janecke D Chitayat J Hahn DM McDonald-McGinn EH Zackai WB Dobyns M Muenke 2009 Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function J Med Genet 46 389 398 10.1136/jmg.2008.063818 19346217 1:CAS:528:DC%2BD1MXps1WitLY%3D
18. CF Lopes F Cendes AM Piovesana F Torres I Lopes-Cendes MA Montenegro MM Guerreiro 2006 Epileptic features of patients with unilateral and bilateral schizencephaly J Child Neurol 21 757 760 10.1177/08830738060210090501 16970881 (Pubitemid 44696724)
19. E Merello E Swanson P De Marco M Akhter P Striano A Rossi A Cama RJ Leventer R Guerrini V Capra WB Dobyns 2008 No major role for the EMX2 gene in schizencephaly Am J Med Genet A 146A 1142 1150 10.1002/ajmg.a.32264 18409201 1:CAS:528:DC%2BD1cXms1OhtLk%3D (Pubitemid 351628600)
20. JE Ming M Muenke 2002 Multiple hits during early embryonic development: digenic diseases and holoprosencephaly Am J Hum Genet 71 1017 1032 10.1086/344412 12395298 1:CAS:528:DC%2BD38XovFOgur4%3D (Pubitemid 35305222)
21. L Nanni JE Ming Y Du RK Hall M Aldred A Bankier M Muenke 2001 SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature Am J Med Genet 102 1 10 10.1002/1096-8628(20010722)102:1<1::AID-AJMG1336>3.0.CO;2-U 11471164 1:STN:280:DC%2BD3MvhvFWqtg%3D%3D (Pubitemid 32623257)
22. E Roessler E Belloni K Gaudenz P Jay P Berta SW Scherer LC Tsui M Muenke 1996 Mutations in the human Sonic Hedgehog gene cause holoprosencephaly Nat Genet 14 357 360 10.1038/ng1196-357 8896572 1:CAS:528:DyaK28XntVCltrY%3D
23. E Roessler F Lacbawan C Dubourg A Paulussen J Herbergs U Hehr C Bendavid N Zhou M Ouspenskaia S Bale S Odent V David M Muenke 2009 The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism Hum Mutat 30 E541 E554 10.1002/humu.20982 19177455
24. E Roessler KB El-Jaick C Dubourg JI Vélez BD Solomon DE Pineda-Alvarez F Lacbawan N Zhou M Ouspenskaia A Paulussen HJ Smeets U Hehr C Bendavid S Bale S Odent V David M Muenke 2009 The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis Hum Mutat 30 E921 E935 10.1002/humu.21090 19603532
25. KA Schachter RS Krauss 2008 Murine models of holoprosencephaly Curr Top Dev Biol 84 139 170 10.1016/S0070-2153(08)00603-0 19186244 1:CAS:528: DC%2BD1MXpsVensL4%3D
26. CC Schell-Apacik B Ertl-Wagner A Panzel K Klausener G Rausch M Muenke H von Voss U Hehr 2009 Maternally inherited heterozygous sequence change in the sonic hedgehog gene in a male patient with bilateral closed-lip schizencephaly and partial absence of the corpus callosum Am J Med Genet A 149A 1592 1594 10.1002/ajmg.a.32940 19533790
27. LA Schimmenti J de la Cruz RA Lewis JD Karkera GS Manligas E Roessler M Muenke 2003 Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia Am J Med Genet A 116A 215 221 10.1002/ajmg.a.10884 12503095 (Pubitemid 36056736)
28. BD Solomon F Lacbawan M Jain S Domené E Roessler C Moore WB Dobyns M Muenke 2009 A novel SIX3 mutation segregates with holoprosencephaly in a large family Am J Med Genet A 149A 919 925 10.1002/ajmg.a.32813 19353631
29. I Tietjen A Bodell K Apse AM Mendonza BS Chang GM Shaw AJ Barkovich EJ Lammer CA Walsh 2007 Comprehensive EMX2 genotyping of a large schizencephaly case series Am J Med Genet A 143A 1313 1316 10.1002/ajmg.a.31767 17506092 1:CAS:528:DC%2BD2sXntlOiu7s%3D (Pubitemid 46870097)
30. J Wang PJ Smith AR Krainer MQ Zhang 2005 Distribution of SR protein exonic splicing enhancer motifs in human protein-coding genes Nucleic Acids Res 33 5053 5062 10.1093/nar/gki810 16147989 1:CAS:528:DC%2BD2MXhtVKhsrzM (Pubitemid 41487813)