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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555002/ http://dx.doi.org/10.1210/js.2019-OR06-6 |
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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 |
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