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Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency
BACKGROUND: To dissect the genetic alteration in two sisters with premature ovarian insufficiency (POI) from a consanguineous family. METHODS: Whole-exome sequencing technology was used in the POI proband, bioinformatics analysis was carried out to identify the potential genetic cause in this pedigr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006558/ https://www.ncbi.nlm.nih.gov/pubmed/29914564 http://dx.doi.org/10.1186/s13048-018-0413-0 |
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author | Chen, Beili Li, Lin Wang, Jing Li, Tengyan Pan, Hong Liu, Beihong Zhou, Yiran Cao, Yunxia Wang, Binbin |
author_facet | Chen, Beili Li, Lin Wang, Jing Li, Tengyan Pan, Hong Liu, Beihong Zhou, Yiran Cao, Yunxia Wang, Binbin |
author_sort | Chen, Beili |
collection | PubMed |
description | BACKGROUND: To dissect the genetic alteration in two sisters with premature ovarian insufficiency (POI) from a consanguineous family. METHODS: Whole-exome sequencing technology was used in the POI proband, bioinformatics analysis was carried out to identify the potential genetic cause in this pedigree. Sanger sequencing analyses were performed to validate the segregation of the variant within the pedigree. In silico analysis was also used to predict the effect and pathogenicity of the variant. RESULTS: Whole-exome sequencing analysis identified novel and rare homozygous mutation associated with POI, namely mutation in FIGLA (c.2 T > C, start codon shift). This homozygous mutation was also harbored by the proband’s sister with POI and was segregated within the consanguineous pedigree. The mutation in the start codon of the FIGLA gene alters the open reading frame, leading to a FIGLA knock-out like phenotype. CONCLUSIONS: Biallelic mutations in FIGLA may be the cause of POI. This study will aid researchers and clinicians in genetic counseling of POI and provides new insights into understanding the mode of genetic inheritance of FIGLA mutations in POI pathology. |
format | Online Article Text |
id | pubmed-6006558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60065582018-06-26 Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency Chen, Beili Li, Lin Wang, Jing Li, Tengyan Pan, Hong Liu, Beihong Zhou, Yiran Cao, Yunxia Wang, Binbin J Ovarian Res Research BACKGROUND: To dissect the genetic alteration in two sisters with premature ovarian insufficiency (POI) from a consanguineous family. METHODS: Whole-exome sequencing technology was used in the POI proband, bioinformatics analysis was carried out to identify the potential genetic cause in this pedigree. Sanger sequencing analyses were performed to validate the segregation of the variant within the pedigree. In silico analysis was also used to predict the effect and pathogenicity of the variant. RESULTS: Whole-exome sequencing analysis identified novel and rare homozygous mutation associated with POI, namely mutation in FIGLA (c.2 T > C, start codon shift). This homozygous mutation was also harbored by the proband’s sister with POI and was segregated within the consanguineous pedigree. The mutation in the start codon of the FIGLA gene alters the open reading frame, leading to a FIGLA knock-out like phenotype. CONCLUSIONS: Biallelic mutations in FIGLA may be the cause of POI. This study will aid researchers and clinicians in genetic counseling of POI and provides new insights into understanding the mode of genetic inheritance of FIGLA mutations in POI pathology. BioMed Central 2018-06-18 /pmc/articles/PMC6006558/ /pubmed/29914564 http://dx.doi.org/10.1186/s13048-018-0413-0 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Chen, Beili Li, Lin Wang, Jing Li, Tengyan Pan, Hong Liu, Beihong Zhou, Yiran Cao, Yunxia Wang, Binbin Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency |
title | Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency |
title_full | Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency |
title_fullStr | Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency |
title_full_unstemmed | Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency |
title_short | Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency |
title_sort | consanguineous familial study revealed biallelic figla mutation associated with premature ovarian insufficiency |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006558/ https://www.ncbi.nlm.nih.gov/pubmed/29914564 http://dx.doi.org/10.1186/s13048-018-0413-0 |
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