Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium
- Autores
- Fofanova Gambetti, Olga V.; Hwa, Vivian; Wit, Jan M.; Domene, Horacio Mario; Argente, Jesús; Bang, Peter; Wolfgang, Hogler; Kirsh, Susan; Pihoker, Catherine; Chiu, Harvey K.; Cohen, Laurie; Jacobsen, Christina; Jasper, Hector Guillermo; Haeusler, Gabriele; Campos Barros, Angel; Gallego Gómez, Elena; Gracia Bouthelier, Ricardo; van Duyvenvoorde, Hermine A.; Pozo, Jesús; Rosenfeld, Ron G.
- Año de publicación
- 2010
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Context: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. Objective: The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. Subjects/Methods: Patient information was derived from the IGFALS Registry, which includes patients with IGFALS mutations and family members who were either heterozygous carriers or homozygous wild-type.Within each family, the effect ofIGFALSmutations on stature was analyzed as follows: 1) effect of two mutant alleles (2ALS) vs. wild-type (WT); 2) effect of two mutant alleles vs. one mutant allele (1ALS); and 3) effect of one mutant allele vs. wild-type. The differences in height SD score (HtSDS) were then pooled and evaluated. Results: Mean HtSDS in 2ALS was 2.31 0.87 (less than 2 SDS in 62%); in 1ALS, 0.83 1.34 (less than 2 SDS in 26%); and in WT, 1.02 1.04 (less than 2 SDS in 12.5%). When analyses were performed within individual families and pooled, the difference in mean HtSDS between 2ALS and WT was 1.93 0.79; between 1ALS and WT, 0.90 1.53; and between 2ALS and 1ALS, 1.48 0.83. Conclusions: Heterozygosity for IGFALS mutations results in approximately 1.0 SD height loss in comparison with wild type, whereas homozygosity or compound heterozygosity gives a further loss of 1.0 to 1.5 SD, suggestive of a gene-dose effect. Further studies involving a larger cohort are needed to evaluate the impact of heterozygous IGFALS mutations not only on auxology, but also on other aspects of the GH/IGF system.
Fil: Fofanova Gambetti, Olga V.. Oregon Health & Science University; Estados Unidos
Fil: Hwa, Vivian. Oregon Health & Science University; Estados Unidos
Fil: Wit, Jan M.. Leiden University. Leiden University Medical Center.; Países Bajos
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina
Fil: Argente, Jesús. Hospital Infantil Universitario Niño Jesús; España. Universidad Autónoma de Madrid; España
Fil: Bang, Peter. Karolinska Institute and University Hospital; Suecia
Fil: Wolfgang, Hogler. Birmingham Children’s Hospital; Reino Unido
Fil: Kirsh, Susan. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Pihoker, Catherine. Children’s Hospital and Regional Medical Center; Estados Unidos
Fil: Chiu, Harvey K.. Children’s Hospital and Regional Medical Center; Estados Unidos
Fil: Cohen, Laurie. Children’s Hospital Boston; Estados Unidos
Fil: Jacobsen, Christina. Children’s Hospital Boston; Estados Unidos
Fil: Jasper, Hector Guillermo. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Haeusler, Gabriele. Medical University of Vienna ; Austria
Fil: Campos Barros, Angel. Hospital Universitario La Paz; España. Instituto de Salud Carlos III; España
Fil: Gallego Gómez, Elena. Hospital Universitario 12 de Octubre; España
Fil: Gracia Bouthelier, Ricardo. Hospital Universitario La Paz; España
Fil: van Duyvenvoorde, Hermine A.. Leiden University. Leiden University Medical Center.; Países Bajos
Fil: Pozo, Jesús. Hospital Infantil Universitario Niño Jesús; España. Universidad Autónoma de Madrid; España
Fil: Rosenfeld, Ron G.. Oregon Health & Science University; Estados Unidos - Materia
-
Acide labile subunit
IGFALS gene mutations
heterozygosity
heterozygous carriers
ALS Consortium
IGFALS Registry - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/103168
Ver los metadatos del registro completo
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Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit ConsortiumFofanova Gambetti, Olga V.Hwa, VivianWit, Jan M.Domene, Horacio MarioArgente, JesúsBang, PeterWolfgang, HoglerKirsh, SusanPihoker, CatherineChiu, Harvey K.Cohen, LaurieJacobsen, ChristinaJasper, Hector GuillermoHaeusler, GabrieleCampos Barros, AngelGallego Gómez, ElenaGracia Bouthelier, Ricardovan Duyvenvoorde, Hermine A.Pozo, JesúsRosenfeld, Ron G.Acide labile subunitIGFALS gene mutationsheterozygosityheterozygous carriersALS ConsortiumIGFALS Registryhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Context: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. Objective: The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. Subjects/Methods: Patient information was derived from the IGFALS Registry, which includes patients with IGFALS mutations and family members who were either heterozygous carriers or homozygous wild-type.Within each family, the effect ofIGFALSmutations on stature was analyzed as follows: 1) effect of two mutant alleles (2ALS) vs. wild-type (WT); 2) effect of two mutant alleles vs. one mutant allele (1ALS); and 3) effect of one mutant allele vs. wild-type. The differences in height SD score (HtSDS) were then pooled and evaluated. Results: Mean HtSDS in 2ALS was 2.31 0.87 (less than 2 SDS in 62%); in 1ALS, 0.83 1.34 (less than 2 SDS in 26%); and in WT, 1.02 1.04 (less than 2 SDS in 12.5%). When analyses were performed within individual families and pooled, the difference in mean HtSDS between 2ALS and WT was 1.93 0.79; between 1ALS and WT, 0.90 1.53; and between 2ALS and 1ALS, 1.48 0.83. Conclusions: Heterozygosity for IGFALS mutations results in approximately 1.0 SD height loss in comparison with wild type, whereas homozygosity or compound heterozygosity gives a further loss of 1.0 to 1.5 SD, suggestive of a gene-dose effect. Further studies involving a larger cohort are needed to evaluate the impact of heterozygous IGFALS mutations not only on auxology, but also on other aspects of the GH/IGF system.Fil: Fofanova Gambetti, Olga V.. Oregon Health & Science University; Estados UnidosFil: Hwa, Vivian. Oregon Health & Science University; Estados UnidosFil: Wit, Jan M.. Leiden University. Leiden University Medical Center.; Países BajosFil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; ArgentinaFil: Argente, Jesús. Hospital Infantil Universitario Niño Jesús; España. Universidad Autónoma de Madrid; EspañaFil: Bang, Peter. Karolinska Institute and University Hospital; SueciaFil: Wolfgang, Hogler. Birmingham Children’s Hospital; Reino UnidoFil: Kirsh, Susan. University Of Toronto. Hospital For Sick Children; CanadáFil: Pihoker, Catherine. Children’s Hospital and Regional Medical Center; Estados UnidosFil: Chiu, Harvey K.. Children’s Hospital and Regional Medical Center; Estados UnidosFil: Cohen, Laurie. Children’s Hospital Boston; Estados UnidosFil: Jacobsen, Christina. Children’s Hospital Boston; Estados UnidosFil: Jasper, Hector Guillermo. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Haeusler, Gabriele. Medical University of Vienna ; AustriaFil: Campos Barros, Angel. Hospital Universitario La Paz; España. Instituto de Salud Carlos III; EspañaFil: Gallego Gómez, Elena. Hospital Universitario 12 de Octubre; EspañaFil: Gracia Bouthelier, Ricardo. Hospital Universitario La Paz; EspañaFil: van Duyvenvoorde, Hermine A.. Leiden University. Leiden University Medical Center.; Países BajosFil: Pozo, Jesús. Hospital Infantil Universitario Niño Jesús; España. Universidad Autónoma de Madrid; EspañaFil: Rosenfeld, Ron G.. Oregon Health & Science University; Estados UnidosEndocrine Society2010-09info: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/11336/103168Fofanova Gambetti, Olga V.; Hwa, Vivian; Wit, Jan M.; Domene, Horacio Mario; Argente, Jesús; et al.; Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 95; 9; 9-2010; 4184-41910021-972X1945-7197CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1210/jc.2010-0489info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jcem/article/95/9/4184/2835276info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:07:36Zoai:ri.conicet.gov.ar:11336/103168instacron: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:34982025-10-15 15:07:36.606CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium |
| title |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium |
| spellingShingle |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium Fofanova Gambetti, Olga V. Acide labile subunit IGFALS gene mutations heterozygosity heterozygous carriers ALS Consortium IGFALS Registry |
| title_short |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium |
| title_full |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium |
| title_fullStr |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium |
| title_full_unstemmed |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium |
| title_sort |
Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium |
| dc.creator.none.fl_str_mv |
Fofanova Gambetti, Olga V. Hwa, Vivian Wit, Jan M. Domene, Horacio Mario Argente, Jesús Bang, Peter Wolfgang, Hogler Kirsh, Susan Pihoker, Catherine Chiu, Harvey K. Cohen, Laurie Jacobsen, Christina Jasper, Hector Guillermo Haeusler, Gabriele Campos Barros, Angel Gallego Gómez, Elena Gracia Bouthelier, Ricardo van Duyvenvoorde, Hermine A. Pozo, Jesús Rosenfeld, Ron G. |
| author |
Fofanova Gambetti, Olga V. |
| author_facet |
Fofanova Gambetti, Olga V. Hwa, Vivian Wit, Jan M. Domene, Horacio Mario Argente, Jesús Bang, Peter Wolfgang, Hogler Kirsh, Susan Pihoker, Catherine Chiu, Harvey K. Cohen, Laurie Jacobsen, Christina Jasper, Hector Guillermo Haeusler, Gabriele Campos Barros, Angel Gallego Gómez, Elena Gracia Bouthelier, Ricardo van Duyvenvoorde, Hermine A. Pozo, Jesús Rosenfeld, Ron G. |
| author_role |
author |
| author2 |
Hwa, Vivian Wit, Jan M. Domene, Horacio Mario Argente, Jesús Bang, Peter Wolfgang, Hogler Kirsh, Susan Pihoker, Catherine Chiu, Harvey K. Cohen, Laurie Jacobsen, Christina Jasper, Hector Guillermo Haeusler, Gabriele Campos Barros, Angel Gallego Gómez, Elena Gracia Bouthelier, Ricardo van Duyvenvoorde, Hermine A. Pozo, Jesús Rosenfeld, Ron G. |
| author2_role |
author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Acide labile subunit IGFALS gene mutations heterozygosity heterozygous carriers ALS Consortium IGFALS Registry |
| topic |
Acide labile subunit IGFALS gene mutations heterozygosity heterozygous carriers ALS Consortium IGFALS Registry |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Context: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. Objective: The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. Subjects/Methods: Patient information was derived from the IGFALS Registry, which includes patients with IGFALS mutations and family members who were either heterozygous carriers or homozygous wild-type.Within each family, the effect ofIGFALSmutations on stature was analyzed as follows: 1) effect of two mutant alleles (2ALS) vs. wild-type (WT); 2) effect of two mutant alleles vs. one mutant allele (1ALS); and 3) effect of one mutant allele vs. wild-type. The differences in height SD score (HtSDS) were then pooled and evaluated. Results: Mean HtSDS in 2ALS was 2.31 0.87 (less than 2 SDS in 62%); in 1ALS, 0.83 1.34 (less than 2 SDS in 26%); and in WT, 1.02 1.04 (less than 2 SDS in 12.5%). When analyses were performed within individual families and pooled, the difference in mean HtSDS between 2ALS and WT was 1.93 0.79; between 1ALS and WT, 0.90 1.53; and between 2ALS and 1ALS, 1.48 0.83. Conclusions: Heterozygosity for IGFALS mutations results in approximately 1.0 SD height loss in comparison with wild type, whereas homozygosity or compound heterozygosity gives a further loss of 1.0 to 1.5 SD, suggestive of a gene-dose effect. Further studies involving a larger cohort are needed to evaluate the impact of heterozygous IGFALS mutations not only on auxology, but also on other aspects of the GH/IGF system. Fil: Fofanova Gambetti, Olga V.. Oregon Health & Science University; Estados Unidos Fil: Hwa, Vivian. Oregon Health & Science University; Estados Unidos Fil: Wit, Jan M.. Leiden University. Leiden University Medical Center.; Países Bajos Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina Fil: Argente, Jesús. Hospital Infantil Universitario Niño Jesús; España. Universidad Autónoma de Madrid; España Fil: Bang, Peter. Karolinska Institute and University Hospital; Suecia Fil: Wolfgang, Hogler. Birmingham Children’s Hospital; Reino Unido Fil: Kirsh, Susan. University Of Toronto. Hospital For Sick Children; Canadá Fil: Pihoker, Catherine. Children’s Hospital and Regional Medical Center; Estados Unidos Fil: Chiu, Harvey K.. Children’s Hospital and Regional Medical Center; Estados Unidos Fil: Cohen, Laurie. Children’s Hospital Boston; Estados Unidos Fil: Jacobsen, Christina. Children’s Hospital Boston; Estados Unidos Fil: Jasper, Hector Guillermo. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Niños "ricardo Gutierrez". Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Haeusler, Gabriele. Medical University of Vienna ; Austria Fil: Campos Barros, Angel. Hospital Universitario La Paz; España. Instituto de Salud Carlos III; España Fil: Gallego Gómez, Elena. Hospital Universitario 12 de Octubre; España Fil: Gracia Bouthelier, Ricardo. Hospital Universitario La Paz; España Fil: van Duyvenvoorde, Hermine A.. Leiden University. Leiden University Medical Center.; Países Bajos Fil: Pozo, Jesús. Hospital Infantil Universitario Niño Jesús; España. Universidad Autónoma de Madrid; España Fil: Rosenfeld, Ron G.. Oregon Health & Science University; Estados Unidos |
| description |
Context: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. Objective: The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. Subjects/Methods: Patient information was derived from the IGFALS Registry, which includes patients with IGFALS mutations and family members who were either heterozygous carriers or homozygous wild-type.Within each family, the effect ofIGFALSmutations on stature was analyzed as follows: 1) effect of two mutant alleles (2ALS) vs. wild-type (WT); 2) effect of two mutant alleles vs. one mutant allele (1ALS); and 3) effect of one mutant allele vs. wild-type. The differences in height SD score (HtSDS) were then pooled and evaluated. Results: Mean HtSDS in 2ALS was 2.31 0.87 (less than 2 SDS in 62%); in 1ALS, 0.83 1.34 (less than 2 SDS in 26%); and in WT, 1.02 1.04 (less than 2 SDS in 12.5%). When analyses were performed within individual families and pooled, the difference in mean HtSDS between 2ALS and WT was 1.93 0.79; between 1ALS and WT, 0.90 1.53; and between 2ALS and 1ALS, 1.48 0.83. Conclusions: Heterozygosity for IGFALS mutations results in approximately 1.0 SD height loss in comparison with wild type, whereas homozygosity or compound heterozygosity gives a further loss of 1.0 to 1.5 SD, suggestive of a gene-dose effect. Further studies involving a larger cohort are needed to evaluate the impact of heterozygous IGFALS mutations not only on auxology, but also on other aspects of the GH/IGF system. |
| publishDate |
2010 |
| dc.date.none.fl_str_mv |
2010-09 |
| 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/11336/103168 Fofanova Gambetti, Olga V.; Hwa, Vivian; Wit, Jan M.; Domene, Horacio Mario; Argente, Jesús; et al.; Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 95; 9; 9-2010; 4184-4191 0021-972X 1945-7197 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/103168 |
| identifier_str_mv |
Fofanova Gambetti, Olga V.; Hwa, Vivian; Wit, Jan M.; Domene, Horacio Mario; Argente, Jesús; et al.; Impact of Heterozygosity for Acid-Labile Subunit (IGFALS) Gene Mutations on Stature: Results from the International Acid-Labile Subunit Consortium; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 95; 9; 9-2010; 4184-4191 0021-972X 1945-7197 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1210/jc.2010-0489 info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jcem/article/95/9/4184/2835276 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf application/pdf |
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Endocrine Society |
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Endocrine Society |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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