STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.

Autores
Scalco, Renata C.; Hwa, Vivian; Domene, Horacio Mario; Jasper, Hector Guillermo; Belgorosky, Alicia; Marino, Roxana; Pereira, Alberto M.; Tonelli, Carlos A.; Wit, Jan M.; Rosenfeld, Ron G.; Jorge, Alexander A. L.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Context and objective: GH insensitivity with immune dysfunction caused by STAT5B mutations is an autosomal recessivecondition. Heterozygous mutations in other genes involved in growth regulation were previously associated with a mildheight reduction. Our objective was to assess for the first time the phenotype of heterozygous STAT5B mutations.Methods: We genotyped and performed clinical and laboratory evaluations in 52 relatives of two previously describedBrazilian brothers with homozygous STAT5B c.424_427del mutation (21 heterozygous). Additionally, we obtained heightdata and genotype from 1104 adult control individuals from the same region in Brazil and identified five additional familiesharboring the same mutation (18 individuals, 11 heterozygous). Furthermore, we gathered the available height data fromfirst-degree relatives of patients with homozygous STAT5B mutations (17 individuals from seven families). Data fromheterozygous individuals and non-carriers were compared.Results: Individuals carrying heterozygous STAT5B c.424_427del mutation were 0.6 SDS shorter than their non-carrierrelatives (PZ0.009). Heterozygous subjects also had significantly lower SDS for serum concentrations of IGF1 (PZ0.028) andIGFBP3 (PZ0.02) than their non-carrier relatives. The 17 heterozygous first-degree relatives of patients carrying homozygousSTAT5B mutations had an average height SDS of K1.4G0.8 when compared with population-matched controls (P! 0.001).Conclusions: STAT5B mutations in the heterozygous state have a significant negative impact on height (w3.9 cm). This effectis milder than the effect seen in the homozygous state, with height usually within the normal range. Our results support thehypothesis that heterozygosity of rare pathogenic variants contributes to normal height heritability.
Fil: Scalco, Renata C.. Universidade de Sao Paulo; Brasil
Fil: Hwa, Vivian. Cincinnati Center for Growth Disorders; Estados Unidos
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marino, Roxana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Pereira, Alberto M.. Leiden University Medical Center; Países Bajos
Fil: Tonelli, Carlos A.. Universidade do Extremo Sul Catarinense; Brasil
Fil: Wit, Jan M.. Leiden University Medical Center; Países Bajos
Fil: Rosenfeld, Ron G.. Oregon Health and Science University; Estados Unidos
Fil: Jorge, Alexander A. L.. Universidade de Sao Paulo; Brasil
Materia
Stat5b
Heterozygous
Mutations
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:11336/8275
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/8275
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.Scalco, Renata C.Hwa, VivianDomene, Horacio MarioJasper, Hector GuillermoBelgorosky, AliciaMarino, RoxanaPereira, Alberto M.Tonelli, Carlos A.Wit, Jan M.Rosenfeld, Ron G.Jorge, Alexander A. L.Stat5bHeterozygousMutationshttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Context and objective: GH insensitivity with immune dysfunction caused by STAT5B mutations is an autosomal recessivecondition. Heterozygous mutations in other genes involved in growth regulation were previously associated with a mildheight reduction. Our objective was to assess for the first time the phenotype of heterozygous STAT5B mutations.Methods: We genotyped and performed clinical and laboratory evaluations in 52 relatives of two previously describedBrazilian brothers with homozygous STAT5B c.424_427del mutation (21 heterozygous). Additionally, we obtained heightdata and genotype from 1104 adult control individuals from the same region in Brazil and identified five additional familiesharboring the same mutation (18 individuals, 11 heterozygous). Furthermore, we gathered the available height data fromfirst-degree relatives of patients with homozygous STAT5B mutations (17 individuals from seven families). Data fromheterozygous individuals and non-carriers were compared.Results: Individuals carrying heterozygous STAT5B c.424_427del mutation were 0.6 SDS shorter than their non-carrierrelatives (PZ0.009). Heterozygous subjects also had significantly lower SDS for serum concentrations of IGF1 (PZ0.028) andIGFBP3 (PZ0.02) than their non-carrier relatives. The 17 heterozygous first-degree relatives of patients carrying homozygousSTAT5B mutations had an average height SDS of K1.4G0.8 when compared with population-matched controls (P! 0.001).Conclusions: STAT5B mutations in the heterozygous state have a significant negative impact on height (w3.9 cm). This effectis milder than the effect seen in the homozygous state, with height usually within the normal range. Our results support thehypothesis that heterozygosity of rare pathogenic variants contributes to normal height heritability.Fil: Scalco, Renata C.. Universidade de Sao Paulo; BrasilFil: Hwa, Vivian. Cincinnati Center for Growth Disorders; Estados UnidosFil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marino, Roxana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Pereira, Alberto M.. Leiden University Medical Center; Países BajosFil: Tonelli, Carlos A.. Universidade do Extremo Sul Catarinense; BrasilFil: Wit, Jan M.. Leiden University Medical Center; Países BajosFil: Rosenfeld, Ron G.. Oregon Health and Science University; Estados UnidosFil: Jorge, Alexander A. L.. Universidade de Sao Paulo; BrasilBioscientifica2015-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8275Scalco, Renata C.; Hwa, Vivian; Domene, Horacio Mario; Jasper, Hector Guillermo; Belgorosky, Alicia; et al.; STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.; Bioscientifica; European Journal Of Endocrinology; 173; 3; 6-2015; 1-170804-4643enginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898761/info:eu-repo/semantics/altIdentifier/doi/10.1530/EJE-15-0398info:eu-repo/semantics/altIdentifier/url/http://www.eje-online.org/content/173/3/291.longinfo:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/26034074/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:30Zoai:ri.conicet.gov.ar:11336/8275instacron: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 09:39:30.869CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
title STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
spellingShingle STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
Scalco, Renata C.
Stat5b
Heterozygous
Mutations
title_short STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
title_full STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
title_fullStr STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
title_full_unstemmed STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
title_sort STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.
dc.creator.none.fl_str_mv Scalco, Renata C.
Hwa, Vivian
Domene, Horacio Mario
Jasper, Hector Guillermo
Belgorosky, Alicia
Marino, Roxana
Pereira, Alberto M.
Tonelli, Carlos A.
Wit, Jan M.
Rosenfeld, Ron G.
Jorge, Alexander A. L.
author Scalco, Renata C.
author_facet Scalco, Renata C.
Hwa, Vivian
Domene, Horacio Mario
Jasper, Hector Guillermo
Belgorosky, Alicia
Marino, Roxana
Pereira, Alberto M.
Tonelli, Carlos A.
Wit, Jan M.
Rosenfeld, Ron G.
Jorge, Alexander A. L.
author_role author
author2 Hwa, Vivian
Domene, Horacio Mario
Jasper, Hector Guillermo
Belgorosky, Alicia
Marino, Roxana
Pereira, Alberto M.
Tonelli, Carlos A.
Wit, Jan M.
Rosenfeld, Ron G.
Jorge, Alexander A. L.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Stat5b
Heterozygous
Mutations
topic Stat5b
Heterozygous
Mutations
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 and objective: GH insensitivity with immune dysfunction caused by STAT5B mutations is an autosomal recessivecondition. Heterozygous mutations in other genes involved in growth regulation were previously associated with a mildheight reduction. Our objective was to assess for the first time the phenotype of heterozygous STAT5B mutations.Methods: We genotyped and performed clinical and laboratory evaluations in 52 relatives of two previously describedBrazilian brothers with homozygous STAT5B c.424_427del mutation (21 heterozygous). Additionally, we obtained heightdata and genotype from 1104 adult control individuals from the same region in Brazil and identified five additional familiesharboring the same mutation (18 individuals, 11 heterozygous). Furthermore, we gathered the available height data fromfirst-degree relatives of patients with homozygous STAT5B mutations (17 individuals from seven families). Data fromheterozygous individuals and non-carriers were compared.Results: Individuals carrying heterozygous STAT5B c.424_427del mutation were 0.6 SDS shorter than their non-carrierrelatives (PZ0.009). Heterozygous subjects also had significantly lower SDS for serum concentrations of IGF1 (PZ0.028) andIGFBP3 (PZ0.02) than their non-carrier relatives. The 17 heterozygous first-degree relatives of patients carrying homozygousSTAT5B mutations had an average height SDS of K1.4G0.8 when compared with population-matched controls (P! 0.001).Conclusions: STAT5B mutations in the heterozygous state have a significant negative impact on height (w3.9 cm). This effectis milder than the effect seen in the homozygous state, with height usually within the normal range. Our results support thehypothesis that heterozygosity of rare pathogenic variants contributes to normal height heritability.
Fil: Scalco, Renata C.. Universidade de Sao Paulo; Brasil
Fil: Hwa, Vivian. Cincinnati Center for Growth Disorders; Estados Unidos
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marino, Roxana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Pereira, Alberto M.. Leiden University Medical Center; Países Bajos
Fil: Tonelli, Carlos A.. Universidade do Extremo Sul Catarinense; Brasil
Fil: Wit, Jan M.. Leiden University Medical Center; Países Bajos
Fil: Rosenfeld, Ron G.. Oregon Health and Science University; Estados Unidos
Fil: Jorge, Alexander A. L.. Universidade de Sao Paulo; Brasil
description Context and objective: GH insensitivity with immune dysfunction caused by STAT5B mutations is an autosomal recessivecondition. Heterozygous mutations in other genes involved in growth regulation were previously associated with a mildheight reduction. Our objective was to assess for the first time the phenotype of heterozygous STAT5B mutations.Methods: We genotyped and performed clinical and laboratory evaluations in 52 relatives of two previously describedBrazilian brothers with homozygous STAT5B c.424_427del mutation (21 heterozygous). Additionally, we obtained heightdata and genotype from 1104 adult control individuals from the same region in Brazil and identified five additional familiesharboring the same mutation (18 individuals, 11 heterozygous). Furthermore, we gathered the available height data fromfirst-degree relatives of patients with homozygous STAT5B mutations (17 individuals from seven families). Data fromheterozygous individuals and non-carriers were compared.Results: Individuals carrying heterozygous STAT5B c.424_427del mutation were 0.6 SDS shorter than their non-carrierrelatives (PZ0.009). Heterozygous subjects also had significantly lower SDS for serum concentrations of IGF1 (PZ0.028) andIGFBP3 (PZ0.02) than their non-carrier relatives. The 17 heterozygous first-degree relatives of patients carrying homozygousSTAT5B mutations had an average height SDS of K1.4G0.8 when compared with population-matched controls (P! 0.001).Conclusions: STAT5B mutations in the heterozygous state have a significant negative impact on height (w3.9 cm). This effectis milder than the effect seen in the homozygous state, with height usually within the normal range. Our results support thehypothesis that heterozygosity of rare pathogenic variants contributes to normal height heritability.
publishDate 2015
dc.date.none.fl_str_mv 2015-06
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/11336/8275
Scalco, Renata C.; Hwa, Vivian; Domene, Horacio Mario; Jasper, Hector Guillermo; Belgorosky, Alicia; et al.; STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.; Bioscientifica; European Journal Of Endocrinology; 173; 3; 6-2015; 1-17
0804-4643
url http://hdl.handle.net/11336/8275
identifier_str_mv Scalco, Renata C.; Hwa, Vivian; Domene, Horacio Mario; Jasper, Hector Guillermo; Belgorosky, Alicia; et al.; STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability.; Bioscientifica; European Journal Of Endocrinology; 173; 3; 6-2015; 1-17
0804-4643
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/PMC4898761/
info:eu-repo/semantics/altIdentifier/doi/10.1530/EJE-15-0398
info:eu-repo/semantics/altIdentifier/url/http://www.eje-online.org/content/173/3/291.long
info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/26034074/
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
application/pdf
dc.publisher.none.fl_str_mv Bioscientifica
publisher.none.fl_str_mv Bioscientifica
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 13.070432

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