Cargando…

OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.

Background: Pituitary Stalk Interruption Syndrome (PSIS) is characterized by the presence of a thin or absent pituitary stalk, usually associated with an ectopic posterior pituitary, hypoplasia of the anterior pituitary and pituitary hormone deficiencies. The identification of pathogenic va...

Descripción completa

Detalles Bibliográficos
Autores principales: Correa, Fernanda, Nakaguma, Marilena, Jorge, Alexander, Funari, Mariana, Lerario, Antonio, Carvalho, Luciani, Arnhold, Ivo, Mendonca, Berenice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555002/
http://dx.doi.org/10.1210/js.2019-OR06-6
_version_ 1783425071253028864
author Correa, Fernanda
Nakaguma, Marilena
Jorge, Alexander
Funari, Mariana
Lerario, Antonio
Carvalho, Luciani
Arnhold, Ivo
Mendonca, Berenice
author_facet Correa, Fernanda
Nakaguma, Marilena
Jorge, Alexander
Funari, Mariana
Lerario, Antonio
Carvalho, Luciani
Arnhold, Ivo
Mendonca, Berenice
author_sort Correa, Fernanda
collection PubMed
description Background: Pituitary Stalk Interruption Syndrome (PSIS) is characterized by the presence of a thin or absent pituitary stalk, usually associated with an ectopic posterior pituitary, hypoplasia of the anterior pituitary and pituitary hormone deficiencies. The identification of pathogenic variants in novel genes has clinical implications for the management of the patients and genetic counseling. Objective: to identify pathogenic variants in patients with PSIS using whole-exome sequencing (WES) (trio approach). Method: We performed whole exome sequencing in eleven patients (trio approach) with PSIS using Agilent Sure Select and Illumina NextSeq technology. The patients had been screened for genes previously associated to hypopituitarism by Sanger or Target gene panel. We searched for pathogenic variants considering de novo, homozygous, compound heterozygous and X- linked inheritance. Results: We identified 116 rare allelic variants (excluding synonymous) located in exons or splice sites: 47 de novo, 20 homozygous, 48 compound heterozygous and 1 X-linked. All variants were expressed in pituitary and/or hypothalamus. Of these, 11 variants were highlighted because the genes had correlation to malformations of central nervous system, midline defects or hormonal deficiencies: LCMT1, PCDHB14, ATXN1, ATXN7, KRT18, SYNE1, WDR27, CC2D2A, HAUS5, IFT140 and ELF4. Among them, five were de novo: two were found in genes associated to cleft palate (LCMT1 and KRT18), two in genes previously associated to neurological phenotype (ATXN7 and ATXN1), one in a gene related to organization of neural cadherin-like cell adhesion (PCDHB14).ELF4 was X-linked and was previously associated with isolated growth hormone deficiency. Conclusion: The WES identified 11 potentially pathogenic variants in new candidate genes for PSIS.
format Online
Article
Text
id pubmed-6555002
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Endocrine Society
record_format MEDLINE/PubMed
spelling pubmed-65550022019-06-13 OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes. Correa, Fernanda Nakaguma, Marilena Jorge, Alexander Funari, Mariana Lerario, Antonio Carvalho, Luciani Arnhold, Ivo Mendonca, Berenice J Endocr Soc Neuroendocrinology and Pituitary Background: Pituitary Stalk Interruption Syndrome (PSIS) is characterized by the presence of a thin or absent pituitary stalk, usually associated with an ectopic posterior pituitary, hypoplasia of the anterior pituitary and pituitary hormone deficiencies. The identification of pathogenic variants in novel genes has clinical implications for the management of the patients and genetic counseling. Objective: to identify pathogenic variants in patients with PSIS using whole-exome sequencing (WES) (trio approach). Method: We performed whole exome sequencing in eleven patients (trio approach) with PSIS using Agilent Sure Select and Illumina NextSeq technology. The patients had been screened for genes previously associated to hypopituitarism by Sanger or Target gene panel. We searched for pathogenic variants considering de novo, homozygous, compound heterozygous and X- linked inheritance. Results: We identified 116 rare allelic variants (excluding synonymous) located in exons or splice sites: 47 de novo, 20 homozygous, 48 compound heterozygous and 1 X-linked. All variants were expressed in pituitary and/or hypothalamus. Of these, 11 variants were highlighted because the genes had correlation to malformations of central nervous system, midline defects or hormonal deficiencies: LCMT1, PCDHB14, ATXN1, ATXN7, KRT18, SYNE1, WDR27, CC2D2A, HAUS5, IFT140 and ELF4. Among them, five were de novo: two were found in genes associated to cleft palate (LCMT1 and KRT18), two in genes previously associated to neurological phenotype (ATXN7 and ATXN1), one in a gene related to organization of neural cadherin-like cell adhesion (PCDHB14).ELF4 was X-linked and was previously associated with isolated growth hormone deficiency. Conclusion: The WES identified 11 potentially pathogenic variants in new candidate genes for PSIS. Endocrine Society 2019-04-30 /pmc/articles/PMC6555002/ http://dx.doi.org/10.1210/js.2019-OR06-6 Text en Copyright © 2019 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Neuroendocrinology and Pituitary
Correa, Fernanda
Nakaguma, Marilena
Jorge, Alexander
Funari, Mariana
Lerario, Antonio
Carvalho, Luciani
Arnhold, Ivo
Mendonca, Berenice
OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.
title OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.
title_full OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.
title_fullStr OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.
title_full_unstemmed OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.
title_short OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.
title_sort or06-6 whole-exome sequencing of patients with pituitary stalk interruption syndrome (psis) reveals probably pathogenic variants in novel candidate genes.
topic Neuroendocrinology and Pituitary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555002/
http://dx.doi.org/10.1210/js.2019-OR06-6
work_keys_str_mv AT correafernanda or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes
AT nakagumamarilena or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes
AT jorgealexander or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes
AT funarimariana or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes
AT lerarioantonio or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes
AT carvalholuciani or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes
AT arnholdivo or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes
AT mendoncaberenice or066wholeexomesequencingofpatientswithpituitarystalkinterruptionsyndromepsisrevealsprobablypathogenicvariantsinnovelcandidategenes