A novel six3 mutation segregates with holoprosencephaly in a large family

Autores
Solomon, Benjamin D.; Lacbawan, Felicitas; Jain, Mahim; Domene, Sabina; Roessler, Erich; Moore, Cynthia; Dobyns, William B.; Muenke, Maximilian
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holopro- sencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from pheno- typically normal adults (non-penetrance) to alobar holoprosen- cephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation.
Fil: Solomon, Benjamin D.. National Institutes of Health; Estados Unidos
Fil: Lacbawan, Felicitas. National Institutes of Health; Estados Unidos. State University of New York; Estados Unidos
Fil: Jain, Mahim. National Institutes of Health; Estados Unidos
Fil: Domene, Sabina. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Roessler, Erich. National Institutes of Health; Estados Unidos
Fil: Moore, Cynthia. Indiana University School of Medicine; Estados Unidos
Fil: Dobyns, William B.. University of Chicago; Estados Unidos
Fil: Muenke, Maximilian. National Institutes of Health; Estados Unidos
Materia
HOLOPROSENCEPHALY
HPE
SIX3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79630
Acceder
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network_name_str CONICET Digital (CONICET)
spelling A novel six3 mutation segregates with holoprosencephaly in a large familySolomon, Benjamin D.Lacbawan, FelicitasJain, MahimDomene, SabinaRoessler, ErichMoore, CynthiaDobyns, William B.Muenke, MaximilianHOLOPROSENCEPHALYHPESIX3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holopro- sencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from pheno- typically normal adults (non-penetrance) to alobar holoprosen- cephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation.Fil: Solomon, Benjamin D.. National Institutes of Health; Estados UnidosFil: Lacbawan, Felicitas. National Institutes of Health; Estados Unidos. State University of New York; Estados UnidosFil: Jain, Mahim. National Institutes of Health; Estados UnidosFil: Domene, Sabina. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Roessler, Erich. National Institutes of Health; Estados UnidosFil: Moore, Cynthia. Indiana University School of Medicine; Estados UnidosFil: Dobyns, William B.. University of Chicago; Estados UnidosFil: Muenke, Maximilian. National Institutes of Health; Estados UnidosWiley-liss, Div John Wiley & Sons Inc2009-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79630Solomon, Benjamin D.; Lacbawan, Felicitas; Jain, Mahim; Domene, Sabina; Roessler, Erich; et al.; A novel six3 mutation segregates with holoprosencephaly in a large family; Wiley-liss, Div John Wiley & Sons Inc; American Journal of Medical Genetics Part A; 149; 5; 5-2009; 919-9251552-4825CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737713/info:eu-repo/semantics/altIdentifier/doi/10.1002/ajmg.a.32813info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.32813info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:22Zoai:ri.conicet.gov.ar:11336/79630instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:48:22.778CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel six3 mutation segregates with holoprosencephaly in a large family
title A novel six3 mutation segregates with holoprosencephaly in a large family
spellingShingle A novel six3 mutation segregates with holoprosencephaly in a large family
Solomon, Benjamin D.
HOLOPROSENCEPHALY
HPE
SIX3
title_short A novel six3 mutation segregates with holoprosencephaly in a large family
title_full A novel six3 mutation segregates with holoprosencephaly in a large family
title_fullStr A novel six3 mutation segregates with holoprosencephaly in a large family
title_full_unstemmed A novel six3 mutation segregates with holoprosencephaly in a large family
title_sort A novel six3 mutation segregates with holoprosencephaly in a large family
dc.creator.none.fl_str_mv Solomon, Benjamin D.
Lacbawan, Felicitas
Jain, Mahim
Domene, Sabina
Roessler, Erich
Moore, Cynthia
Dobyns, William B.
Muenke, Maximilian
author Solomon, Benjamin D.
author_facet Solomon, Benjamin D.
Lacbawan, Felicitas
Jain, Mahim
Domene, Sabina
Roessler, Erich
Moore, Cynthia
Dobyns, William B.
Muenke, Maximilian
author_role author
author2 Lacbawan, Felicitas
Jain, Mahim
Domene, Sabina
Roessler, Erich
Moore, Cynthia
Dobyns, William B.
Muenke, Maximilian
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HOLOPROSENCEPHALY
HPE
SIX3
topic HOLOPROSENCEPHALY
HPE
SIX3
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holopro- sencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from pheno- typically normal adults (non-penetrance) to alobar holoprosen- cephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation.
Fil: Solomon, Benjamin D.. National Institutes of Health; Estados Unidos
Fil: Lacbawan, Felicitas. National Institutes of Health; Estados Unidos. State University of New York; Estados Unidos
Fil: Jain, Mahim. National Institutes of Health; Estados Unidos
Fil: Domene, Sabina. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Roessler, Erich. National Institutes of Health; Estados Unidos
Fil: Moore, Cynthia. Indiana University School of Medicine; Estados Unidos
Fil: Dobyns, William B.. University of Chicago; Estados Unidos
Fil: Muenke, Maximilian. National Institutes of Health; Estados Unidos
description Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holopro- sencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from pheno- typically normal adults (non-penetrance) to alobar holoprosen- cephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation.
publishDate 2009
dc.date.none.fl_str_mv 2009-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79630
Solomon, Benjamin D.; Lacbawan, Felicitas; Jain, Mahim; Domene, Sabina; Roessler, Erich; et al.; A novel six3 mutation segregates with holoprosencephaly in a large family; Wiley-liss, Div John Wiley & Sons Inc; American Journal of Medical Genetics Part A; 149; 5; 5-2009; 919-925
1552-4825
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79630
identifier_str_mv Solomon, Benjamin D.; Lacbawan, Felicitas; Jain, Mahim; Domene, Sabina; Roessler, Erich; et al.; A novel six3 mutation segregates with holoprosencephaly in a large family; Wiley-liss, Div John Wiley & Sons Inc; American Journal of Medical Genetics Part A; 149; 5; 5-2009; 919-925
1552-4825
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737713/
info:eu-repo/semantics/altIdentifier/doi/10.1002/ajmg.a.32813
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.32813
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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