Genetics of combined pituitary hormone deficiency: Roadmap into the genome era

Autores
Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; Cheung, Leonard Y.M.; Daly, Alexandre Z.; Ajmal, Adnan; Pérez Millán, María Inés; Bilge Ozel, A.; Kitzman, Jacob; Mills, Ryan E.; Li, Jun Z.; Camper, Sally
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. Weexpect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity.Wediscuss approaches for future research in the genetics of CPHD.
Fil: Fang, Qing. University of Michigan; Estados Unidos
Fil: George, Akima S.. University of Michigan; Estados Unidos
Fil: Brinkmeier, Michelle L.. University of Michigan; Estados Unidos
Fil: Mortensen, Amanda H.. University of Michigan; Estados Unidos
Fil: Gergics, Peter. University of Michigan; Estados Unidos
Fil: Cheung, Leonard Y.M.. University of Michigan; Estados Unidos
Fil: Daly, Alexandre Z.. University of Michigan; Estados Unidos
Fil: Ajmal, Adnan. University of Michigan; Estados Unidos
Fil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bilge Ozel, A.. University of Michigan; Estados Unidos
Fil: Kitzman, Jacob. University of Michigan; Estados Unidos
Fil: Mills, Ryan E.. University of Michigan; Estados Unidos
Fil: Li, Jun Z.. University of Michigan; Estados Unidos
Fil: Camper, Sally. University of Michigan; Estados Unidos
Materia
Hipopituitarism
Human Genetics
Sequecing
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:11336/116202
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/116202
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Genetics of combined pituitary hormone deficiency: Roadmap into the genome eraFang, QingGeorge, Akima S.Brinkmeier, Michelle L.Mortensen, Amanda H.Gergics, PeterCheung, Leonard Y.M.Daly, Alexandre Z.Ajmal, AdnanPérez Millán, María InésBilge Ozel, A.Kitzman, JacobMills, Ryan E.Li, Jun Z.Camper, SallyHipopituitarismHuman GeneticsSequecingMutationshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. Weexpect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity.Wediscuss approaches for future research in the genetics of CPHD.Fil: Fang, Qing. University of Michigan; Estados UnidosFil: George, Akima S.. University of Michigan; Estados UnidosFil: Brinkmeier, Michelle L.. University of Michigan; Estados UnidosFil: Mortensen, Amanda H.. University of Michigan; Estados UnidosFil: Gergics, Peter. University of Michigan; Estados UnidosFil: Cheung, Leonard Y.M.. University of Michigan; Estados UnidosFil: Daly, Alexandre Z.. University of Michigan; Estados UnidosFil: Ajmal, Adnan. University of Michigan; Estados UnidosFil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Bilge Ozel, A.. University of Michigan; Estados UnidosFil: Kitzman, Jacob. University of Michigan; Estados UnidosFil: Mills, Ryan E.. University of Michigan; Estados UnidosFil: Li, Jun Z.. University of Michigan; Estados UnidosFil: Camper, Sally. University of Michigan; Estados UnidosEndocrine Society2016-12info: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/11336/116202Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; et al.; Genetics of combined pituitary hormone deficiency: Roadmap into the genome era; Endocrine Society; Endocrine Reviews; 37; 6; 12-2016; 636-6750163-769X1945-7189CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155665/info:eu-repo/semantics/altIdentifier/doi/10.1210/er.2016-1101info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/edrv/article/37/6/636/2691717info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T10:22:05Zoai:ri.conicet.gov.ar:11336/116202instacron: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:34982026-02-26 10:22:06.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
title Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
spellingShingle Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
Fang, Qing
Hipopituitarism
Human Genetics
Sequecing
Mutations
title_short Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
title_full Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
title_fullStr Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
title_full_unstemmed Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
title_sort Genetics of combined pituitary hormone deficiency: Roadmap into the genome era
dc.creator.none.fl_str_mv Fang, Qing
George, Akima S.
Brinkmeier, Michelle L.
Mortensen, Amanda H.
Gergics, Peter
Cheung, Leonard Y.M.
Daly, Alexandre Z.
Ajmal, Adnan
Pérez Millán, María Inés
Bilge Ozel, A.
Kitzman, Jacob
Mills, Ryan E.
Li, Jun Z.
Camper, Sally
author Fang, Qing
author_facet Fang, Qing
George, Akima S.
Brinkmeier, Michelle L.
Mortensen, Amanda H.
Gergics, Peter
Cheung, Leonard Y.M.
Daly, Alexandre Z.
Ajmal, Adnan
Pérez Millán, María Inés
Bilge Ozel, A.
Kitzman, Jacob
Mills, Ryan E.
Li, Jun Z.
Camper, Sally
author_role author
author2 George, Akima S.
Brinkmeier, Michelle L.
Mortensen, Amanda H.
Gergics, Peter
Cheung, Leonard Y.M.
Daly, Alexandre Z.
Ajmal, Adnan
Pérez Millán, María Inés
Bilge Ozel, A.
Kitzman, Jacob
Mills, Ryan E.
Li, Jun Z.
Camper, Sally
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hipopituitarism
Human Genetics
Sequecing
Mutations
topic Hipopituitarism
Human Genetics
Sequecing
Mutations
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. Weexpect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity.Wediscuss approaches for future research in the genetics of CPHD.
Fil: Fang, Qing. University of Michigan; Estados Unidos
Fil: George, Akima S.. University of Michigan; Estados Unidos
Fil: Brinkmeier, Michelle L.. University of Michigan; Estados Unidos
Fil: Mortensen, Amanda H.. University of Michigan; Estados Unidos
Fil: Gergics, Peter. University of Michigan; Estados Unidos
Fil: Cheung, Leonard Y.M.. University of Michigan; Estados Unidos
Fil: Daly, Alexandre Z.. University of Michigan; Estados Unidos
Fil: Ajmal, Adnan. University of Michigan; Estados Unidos
Fil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bilge Ozel, A.. University of Michigan; Estados Unidos
Fil: Kitzman, Jacob. University of Michigan; Estados Unidos
Fil: Mills, Ryan E.. University of Michigan; Estados Unidos
Fil: Li, Jun Z.. University of Michigan; Estados Unidos
Fil: Camper, Sally. University of Michigan; Estados Unidos
description The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. Weexpect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity.Wediscuss approaches for future research in the genetics of CPHD.
publishDate 2016
dc.date.none.fl_str_mv 2016-12
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/11336/116202
Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; et al.; Genetics of combined pituitary hormone deficiency: Roadmap into the genome era; Endocrine Society; Endocrine Reviews; 37; 6; 12-2016; 636-675
0163-769X
1945-7189
CONICET Digital
CONICET
url http://hdl.handle.net/11336/116202
identifier_str_mv Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; et al.; Genetics of combined pituitary hormone deficiency: Roadmap into the genome era; Endocrine Society; Endocrine Reviews; 37; 6; 12-2016; 636-675
0163-769X
1945-7189
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/PMC5155665/
info:eu-repo/semantics/altIdentifier/doi/10.1210/er.2016-1101
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/edrv/article/37/6/636/2691717
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 Endocrine Society
publisher.none.fl_str_mv Endocrine Society
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 13.176822

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