Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B

Palencia-Campos, Adrián; Martinez-Fernandez, Maria Luisa; Altunoglu, Umut; Soto-Bielicka, Patricia; Torres, Antonio; Marín, Purificación; Aller, Elena; Şentürk, Leyli; Berköz, Ömer; Yıldıran, Mehmet; Kayserili, Hülya; Gil-Camarero, Elena; Colli-Lista, Gloria; Sanchís-Calvo, Amparo; Carretero, Alba; ECEMC Working Group on Polydactyly; Guillén-Navarro, Encarna; López-González, Vanesa; Ballesta-Martínez, María; Rosell, Jordi; Aglan, Mona S; Temtamy, Samia; Otaify, Ghada A; Cuevas Catalina, María Lourdes; Torres-Saavedra, María-Nieves; Nevado, Julián; Tenorio, Jair; Lapunzina, Pablo; Bermejo-Sanchez, Eva; Ruiz-Pérez, Víctor L

Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B

Postaxial polydactyly (PAP) is a frequent limb malformation consisting in the duplication of the fifth digit of the hand or foot. Morphologically, this condition is divided into type A and B, with PAP-B corresponding to a more rudimentary extra-digit. Recently, biallelic truncating variants in the t...

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Autores:	Palencia-Campos, Adrián, Martinez-Fernandez, Maria Luisa, Altunoglu, Umut, Soto-Bielicka, Patricia, Torres, Antonio, Marín, Purificación, Aller, Elena, Şentürk, Leyli, Berköz, Ömer, Yıldıran, Mehmet, Kayserili, Hülya, Gil-Camarero, Elena, Colli-Lista, Gloria, Sanchís-Calvo, Amparo, Carretero, Alba, ECEMC Working Group on Polydactyly, Guillén-Navarro, Encarna, López-González, Vanesa, Ballesta-Martínez, María, Rosell, Jordi, Aglan, Mona S, Temtamy, Samia, Otaify, Ghada A, Cuevas Catalina, María Lourdes, Torres-Saavedra, María-Nieves, Nevado, Julián, Tenorio, Jair, Lapunzina, Pablo, Bermejo-Sanchez, Eva, Ruiz-Pérez, Víctor L
Tipo de recurso:	artículo
Fecha de publicación:	2020
País:	España
Institución:	Instituto de Salud Carlos III (ISCIII)
Repositorio:	Repisalud
Idioma:	inglés
OAI Identifier:	oai:repisalud.isciii.es:20.500.12105/26037
Acceso en línea:	https://hdl.handle.net/20.500.12105/26037
Access Level:	acceso abierto
Palabra clave:	GLI1 Hedgehog signaling Incomplete penetrance Limb development Postaxial polydactyly A/B Alleles Amino Acid Substitution Female Fibroblasts Fingers Gene Expression Genes, Dominant Genes, Reporter Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Heterozygote Humans Infant Infant, Newborn Male Pedigree Phenotype Polydactyly Polymorphism, Single Nucleotide Sequence Analysis, DNA Toes Zinc Finger Protein GLI1

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network_acronym_str	ES
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spelling	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/BPalencia-Campos, AdriánMartinez-Fernandez, Maria LuisaAltunoglu, UmutSoto-Bielicka, PatriciaTorres, AntonioMarín, PurificaciónAller, ElenaŞentürk, LeyliBerköz, ÖmerYıldıran, MehmetKayserili, HülyaGil-Camarero, ElenaColli-Lista, GloriaSanchís-Calvo, AmparoCarretero, AlbaECEMC Working Group on PolydactylyGuillén-Navarro, EncarnaLópez-González, VanesaBallesta-Martínez, MaríaRosell, JordiAglan, Mona STemtamy, SamiaOtaify, Ghada ACuevas Catalina, María LourdesTorres-Saavedra, María-NievesNevado, JuliánTenorio, JairLapunzina, PabloBermejo-Sanchez, EvaRuiz-Pérez, Víctor LGLI1Hedgehog signalingIncomplete penetranceLimb developmentPostaxial polydactyly A/BAllelesAmino Acid SubstitutionFemaleFibroblastsFingersGene ExpressionGenes, DominantGenes, ReporterGenetic Association StudiesGenetic Predisposition to DiseaseGenetic VariationGenotypeHeterozygoteHumansInfantInfant, NewbornMalePedigreePhenotypePolydactylyPolymorphism, Single NucleotideSequence Analysis, DNAToesZinc Finger Protein GLI1Postaxial polydactyly (PAP) is a frequent limb malformation consisting in the duplication of the fifth digit of the hand or foot. Morphologically, this condition is divided into type A and B, with PAP-B corresponding to a more rudimentary extra-digit. Recently, biallelic truncating variants in the transcription factor GLI1 were reported to be associated with a recessive disorder, which in addition to PAP-A, may include syndromic features. Moreover, two heterozygous subjects carrying only one inactive copy of GLI1 were also identified with PAP. Herein, we aimed to determine the level of involvement of GLI1 in isolated PAP, a condition previously established to be autosomal dominantly inherited with incomplete penetrance. We analyzed the coding region of GLI1 in 95 independent probands with nonsyndromic PAP and found 11.57% of these subjects with single heterozygous pathogenic variants in this gene. The detected variants lead to premature termination codons or result in amino acid changes in the DNA-binding domain of GLI1 that diminish its transactivation activity. Family segregation analysis of these variants was consistent with dominant inheritance with incomplete penetrance. We conclude that heterozygous changes in GLI1 underlie a significant proportion of sporadic or familial cases of isolated PAP-A/B.WileyMinisterio de Economía y Competitividad (España)Instituto de Salud Carlos IIIMinisterio de Ciencia, Innovación y Universidades (España)Fundación 1000 sobre Defectos Congénitos20252025-01-1620202020-01-0120202020-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12105/26037reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES SAF2016–75434‐R Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/260372026-06-12T12:43:37Z
dc.title.none.fl_str_mv	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
title	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
spellingShingle	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B Palencia-Campos, Adrián GLI1 Hedgehog signaling Incomplete penetrance Limb development Postaxial polydactyly A/B Alleles Amino Acid Substitution Female Fibroblasts Fingers Gene Expression Genes, Dominant Genes, Reporter Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Heterozygote Humans Infant Infant, Newborn Male Pedigree Phenotype Polydactyly Polymorphism, Single Nucleotide Sequence Analysis, DNA Toes Zinc Finger Protein GLI1
title_short	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
title_full	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
title_fullStr	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
title_full_unstemmed	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
title_sort	Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B
dc.creator.none.fl_str_mv	Palencia-Campos, Adrián Martinez-Fernandez, Maria Luisa Altunoglu, Umut Soto-Bielicka, Patricia Torres, Antonio Marín, Purificación Aller, Elena Şentürk, Leyli Berköz, Ömer Yıldıran, Mehmet Kayserili, Hülya Gil-Camarero, Elena Colli-Lista, Gloria Sanchís-Calvo, Amparo Carretero, Alba ECEMC Working Group on Polydactyly Guillén-Navarro, Encarna López-González, Vanesa Ballesta-Martínez, María Rosell, Jordi Aglan, Mona S Temtamy, Samia Otaify, Ghada A Cuevas Catalina, María Lourdes Torres-Saavedra, María-Nieves Nevado, Julián Tenorio, Jair Lapunzina, Pablo Bermejo-Sanchez, Eva Ruiz-Pérez, Víctor L
author	Palencia-Campos, Adrián
author_facet	Palencia-Campos, Adrián Martinez-Fernandez, Maria Luisa Altunoglu, Umut Soto-Bielicka, Patricia Torres, Antonio Marín, Purificación Aller, Elena Şentürk, Leyli Berköz, Ömer Yıldıran, Mehmet Kayserili, Hülya Gil-Camarero, Elena Colli-Lista, Gloria Sanchís-Calvo, Amparo Carretero, Alba ECEMC Working Group on Polydactyly Guillén-Navarro, Encarna López-González, Vanesa Ballesta-Martínez, María Rosell, Jordi Aglan, Mona S Temtamy, Samia Otaify, Ghada A Cuevas Catalina, María Lourdes Torres-Saavedra, María-Nieves Nevado, Julián Tenorio, Jair Lapunzina, Pablo Bermejo-Sanchez, Eva Ruiz-Pérez, Víctor L
author_role	author
author2	Martinez-Fernandez, Maria Luisa Altunoglu, Umut Soto-Bielicka, Patricia Torres, Antonio Marín, Purificación Aller, Elena Şentürk, Leyli Berköz, Ömer Yıldıran, Mehmet Kayserili, Hülya Gil-Camarero, Elena Colli-Lista, Gloria Sanchís-Calvo, Amparo Carretero, Alba ECEMC Working Group on Polydactyly Guillén-Navarro, Encarna López-González, Vanesa Ballesta-Martínez, María Rosell, Jordi Aglan, Mona S Temtamy, Samia Otaify, Ghada A Cuevas Catalina, María Lourdes Torres-Saavedra, María-Nieves Nevado, Julián Tenorio, Jair Lapunzina, Pablo Bermejo-Sanchez, Eva Ruiz-Pérez, Víctor L
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Ministerio de Economía y Competitividad (España) Instituto de Salud Carlos III Ministerio de Ciencia, Innovación y Universidades (España) Fundación 1000 sobre Defectos Congénitos
dc.subject.none.fl_str_mv	GLI1 Hedgehog signaling Incomplete penetrance Limb development Postaxial polydactyly A/B Alleles Amino Acid Substitution Female Fibroblasts Fingers Gene Expression Genes, Dominant Genes, Reporter Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Heterozygote Humans Infant Infant, Newborn Male Pedigree Phenotype Polydactyly Polymorphism, Single Nucleotide Sequence Analysis, DNA Toes Zinc Finger Protein GLI1
topic	GLI1 Hedgehog signaling Incomplete penetrance Limb development Postaxial polydactyly A/B Alleles Amino Acid Substitution Female Fibroblasts Fingers Gene Expression Genes, Dominant Genes, Reporter Genetic Association Studies Genetic Predisposition to Disease Genetic Variation Genotype Heterozygote Humans Infant Infant, Newborn Male Pedigree Phenotype Polydactyly Polymorphism, Single Nucleotide Sequence Analysis, DNA Toes Zinc Finger Protein GLI1
description	Postaxial polydactyly (PAP) is a frequent limb malformation consisting in the duplication of the fifth digit of the hand or foot. Morphologically, this condition is divided into type A and B, with PAP-B corresponding to a more rudimentary extra-digit. Recently, biallelic truncating variants in the transcription factor GLI1 were reported to be associated with a recessive disorder, which in addition to PAP-A, may include syndromic features. Moreover, two heterozygous subjects carrying only one inactive copy of GLI1 were also identified with PAP. Herein, we aimed to determine the level of involvement of GLI1 in isolated PAP, a condition previously established to be autosomal dominantly inherited with incomplete penetrance. We analyzed the coding region of GLI1 in 95 independent probands with nonsyndromic PAP and found 11.57% of these subjects with single heterozygous pathogenic variants in this gene. The detected variants lead to premature termination codons or result in amino acid changes in the DNA-binding domain of GLI1 that diminish its transactivation activity. Family segregation analysis of these variants was consistent with dominant inheritance with incomplete penetrance. We conclude that heterozygous changes in GLI1 underlie a significant proportion of sporadic or familial cases of isolated PAP-A/B.
publishDate	2020
dc.date.none.fl_str_mv	2020 2020-01-01 2020 2020-01-01 2025 2025-01-16
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/20.500.12105/26037
url	https://hdl.handle.net/20.500.12105/26037
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	ES SAF2016–75434‐R Not available
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	Wiley
publisher.none.fl_str_mv	Wiley
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15.811543

Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B

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