SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1093/hmg/ddm204 http://hdl.handle.net/11449/231047 |
Resumo: | We ascertained three different families affected with oto-dental syndrome, a rare but severe autosomal-dominant craniofacial anomaly. All affected patients had the unique phenotype of grossly enlarged molar teeth (globodontia) segregating with a high-frequency sensorineural hearing loss. In addition, ocular coloboma segregated with disease in one family (oculo-oto-dental syndrome). A genome-wide scan was performed using the Affymetrix GeneChip10K 2.0 Array. Parametric linkage analysis gave a single LOD score peak of 3.9 identifying linkage to chromosome 11q13. Haplotype analysis revealed three obligatory recombination events defining a 4.8 Mb linked interval between D11S1889 and SNP rs2077955. Higher resolution mapping and Southern blot analysis in each family identified overlapping hemizygous microdeletions. SNP expression analysis and real-time quantitative RT-PCR in patient lymphoblast cell lines excluded a positional effect on the flanking genes ORAOV1, PPFIA1 and CTTN. The smallest 43 kb deletion resulted in the loss of only one gene, FGF3, which was also deleted in all other otodental families. These data suggest that FGF3 haploinsufficiency is likely to be the cause of otodental syndrome. In addition, the Fas-associated death domain (FADD) gene was also deleted in the one family segregating ocular coloboma. Spatiotemporal in situ hybridization in zebrafish embryos established for the first time that fadd is expressed during eye development. We therefore propose that FADD haploinsufficiency is likely to be responsible for ocular coloboma in this family. This study therefore implicates FGF3 and FADD in human craniofacial disease. © The Author 2007. Published by Oxford University Press. All rights reserved. |
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SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular colobomaWe ascertained three different families affected with oto-dental syndrome, a rare but severe autosomal-dominant craniofacial anomaly. All affected patients had the unique phenotype of grossly enlarged molar teeth (globodontia) segregating with a high-frequency sensorineural hearing loss. In addition, ocular coloboma segregated with disease in one family (oculo-oto-dental syndrome). A genome-wide scan was performed using the Affymetrix GeneChip10K 2.0 Array. Parametric linkage analysis gave a single LOD score peak of 3.9 identifying linkage to chromosome 11q13. Haplotype analysis revealed three obligatory recombination events defining a 4.8 Mb linked interval between D11S1889 and SNP rs2077955. Higher resolution mapping and Southern blot analysis in each family identified overlapping hemizygous microdeletions. SNP expression analysis and real-time quantitative RT-PCR in patient lymphoblast cell lines excluded a positional effect on the flanking genes ORAOV1, PPFIA1 and CTTN. The smallest 43 kb deletion resulted in the loss of only one gene, FGF3, which was also deleted in all other otodental families. These data suggest that FGF3 haploinsufficiency is likely to be the cause of otodental syndrome. In addition, the Fas-associated death domain (FADD) gene was also deleted in the one family segregating ocular coloboma. Spatiotemporal in situ hybridization in zebrafish embryos established for the first time that fadd is expressed during eye development. We therefore propose that FADD haploinsufficiency is likely to be responsible for ocular coloboma in this family. This study therefore implicates FGF3 and FADD in human craniofacial disease. © The Author 2007. Published by Oxford University Press. All rights reserved.Department of Clinical Neuroscience Imperial College London, St Dunstan's Road, London W6 8RPCSC-IC Microarray Centre/Genome Centre Imperial College London, St Dunstan's Road, London W6 8RPNHLI Imperial College London, St Dunstan's Road, London SW7 2AZFaculte de Chirgurgie Dentaire Universite Louis Pasteur, Strasbourg F-67000Max Delbrück Center for Molecular Medicine, D-13092 BerlinDepartment of Paediatric Dentistry Araraquara Dental School University of São Paulo State, São Paulo 14801-903Department of Oral and Maxillofacial Surgery Free University of Brussels, 1050 ElseneImperial College LondonUniversite Louis PasteurMax Delbrück Center for Molecular MedicineUniversidade de São Paulo (USP)Free University of BrusselsGregory-Evans, Cheryl Y.Moosajee, MariyaHodges, Matthew D.Mackay, Donna S.Game, LaurenceVargesson, NeilBloch-Zupan, AgnèsRüschendorf, FranzSantos-Pinto, LourdesWackens, GeorgesGregory-Evans, Kevin2022-04-29T08:43:21Z2022-04-29T08:43:21Z2007-10-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2482-2493http://dx.doi.org/10.1093/hmg/ddm204Human Molecular Genetics, v. 16, n. 20, p. 2482-2493, 2007.0964-69061460-2083http://hdl.handle.net/11449/23104710.1093/hmg/ddm2042-s2.0-34848817416Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengHuman Molecular Geneticsinfo:eu-repo/semantics/openAccess2022-04-29T08:43:21Zoai:repositorio.unesp.br:11449/231047Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-06T00:05:43.260098Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma |
title |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma |
spellingShingle |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma Gregory-Evans, Cheryl Y. |
title_short |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma |
title_full |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma |
title_fullStr |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma |
title_full_unstemmed |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma |
title_sort |
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma |
author |
Gregory-Evans, Cheryl Y. |
author_facet |
Gregory-Evans, Cheryl Y. Moosajee, Mariya Hodges, Matthew D. Mackay, Donna S. Game, Laurence Vargesson, Neil Bloch-Zupan, Agnès Rüschendorf, Franz Santos-Pinto, Lourdes Wackens, Georges Gregory-Evans, Kevin |
author_role |
author |
author2 |
Moosajee, Mariya Hodges, Matthew D. Mackay, Donna S. Game, Laurence Vargesson, Neil Bloch-Zupan, Agnès Rüschendorf, Franz Santos-Pinto, Lourdes Wackens, Georges Gregory-Evans, Kevin |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Imperial College London Universite Louis Pasteur Max Delbrück Center for Molecular Medicine Universidade de São Paulo (USP) Free University of Brussels |
dc.contributor.author.fl_str_mv |
Gregory-Evans, Cheryl Y. Moosajee, Mariya Hodges, Matthew D. Mackay, Donna S. Game, Laurence Vargesson, Neil Bloch-Zupan, Agnès Rüschendorf, Franz Santos-Pinto, Lourdes Wackens, Georges Gregory-Evans, Kevin |
description |
We ascertained three different families affected with oto-dental syndrome, a rare but severe autosomal-dominant craniofacial anomaly. All affected patients had the unique phenotype of grossly enlarged molar teeth (globodontia) segregating with a high-frequency sensorineural hearing loss. In addition, ocular coloboma segregated with disease in one family (oculo-oto-dental syndrome). A genome-wide scan was performed using the Affymetrix GeneChip10K 2.0 Array. Parametric linkage analysis gave a single LOD score peak of 3.9 identifying linkage to chromosome 11q13. Haplotype analysis revealed three obligatory recombination events defining a 4.8 Mb linked interval between D11S1889 and SNP rs2077955. Higher resolution mapping and Southern blot analysis in each family identified overlapping hemizygous microdeletions. SNP expression analysis and real-time quantitative RT-PCR in patient lymphoblast cell lines excluded a positional effect on the flanking genes ORAOV1, PPFIA1 and CTTN. The smallest 43 kb deletion resulted in the loss of only one gene, FGF3, which was also deleted in all other otodental families. These data suggest that FGF3 haploinsufficiency is likely to be the cause of otodental syndrome. In addition, the Fas-associated death domain (FADD) gene was also deleted in the one family segregating ocular coloboma. Spatiotemporal in situ hybridization in zebrafish embryos established for the first time that fadd is expressed during eye development. We therefore propose that FADD haploinsufficiency is likely to be responsible for ocular coloboma in this family. This study therefore implicates FGF3 and FADD in human craniofacial disease. © The Author 2007. Published by Oxford University Press. All rights reserved. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-10-15 2022-04-29T08:43:21Z 2022-04-29T08:43:21Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1093/hmg/ddm204 Human Molecular Genetics, v. 16, n. 20, p. 2482-2493, 2007. 0964-6906 1460-2083 http://hdl.handle.net/11449/231047 10.1093/hmg/ddm204 2-s2.0-34848817416 |
url |
http://dx.doi.org/10.1093/hmg/ddm204 http://hdl.handle.net/11449/231047 |
identifier_str_mv |
Human Molecular Genetics, v. 16, n. 20, p. 2482-2493, 2007. 0964-6906 1460-2083 10.1093/hmg/ddm204 2-s2.0-34848817416 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Human Molecular Genetics |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
2482-2493 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808128241935843328 |