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Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis
PURPOSE: Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis, affecting 0.05–0.5% population. The aim of the study was an identification of genetic factors responsible for thyroid maldevelopment in two siblings with THA. METHODS: We evaluated a thr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881956/ https://www.ncbi.nlm.nih.gov/pubmed/32696176 http://dx.doi.org/10.1007/s12020-020-02422-1 |
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author | Szczepanek-Parulska, Ewelina Budny, Bartłomiej Borowczyk, Martyna Zawadzka, Katarzyna Sztromwasser, Paweł Ruchała, Marek |
author_facet | Szczepanek-Parulska, Ewelina Budny, Bartłomiej Borowczyk, Martyna Zawadzka, Katarzyna Sztromwasser, Paweł Ruchała, Marek |
author_sort | Szczepanek-Parulska, Ewelina |
collection | PubMed |
description | PURPOSE: Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis, affecting 0.05–0.5% population. The aim of the study was an identification of genetic factors responsible for thyroid maldevelopment in two siblings with THA. METHODS: We evaluated a three-generation THA family with two sisters presenting the disorder. Proband (Patient II:3) was diagnosed at the age of 45 due to neck asymmetry. Left lobe agenesis and nontoxic multinodular goiter were depicted. Proband’s sister (Patient II:6) was euthyroid, showed up at the age of 39 due to neck discomfort and left-sided THA was demonstrated. Affected individuals were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Kit) and all identified variants were evaluated for pathogenicity. Sanger sequencing was used to confirm WES data and check segregation among first-degree relatives. RESULTS: In both siblings, a compound heterozygous mutations NM_000168.6: c.[2179G>A];[4039C>A] (NP_000159.3: p.[Gly727Arg];[Gln1347Lys]) were identified in the GLI3 gene, affecting exon 14 and 15, respectively. According to the American College of Medical Genetics, variants are classified as of uncertain significance, and were found to be very rare (GnomAD MAF 0.007131 and 0.00003187). The segregation mapping and analysis of relatives indicated causativeness of compound heterozygosity. CONCLUSIONS: We demonstrated for the first time a unique association of THA phenotype and the presence of compound heterozygous mutations p.[Gly727Arg];[Gln1347Lys] of GLI3 gene in two siblings. |
format | Online Article Text |
id | pubmed-7881956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-78819562021-02-25 Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis Szczepanek-Parulska, Ewelina Budny, Bartłomiej Borowczyk, Martyna Zawadzka, Katarzyna Sztromwasser, Paweł Ruchała, Marek Endocrine Endocrine Genetics/Epigenetics PURPOSE: Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis, affecting 0.05–0.5% population. The aim of the study was an identification of genetic factors responsible for thyroid maldevelopment in two siblings with THA. METHODS: We evaluated a three-generation THA family with two sisters presenting the disorder. Proband (Patient II:3) was diagnosed at the age of 45 due to neck asymmetry. Left lobe agenesis and nontoxic multinodular goiter were depicted. Proband’s sister (Patient II:6) was euthyroid, showed up at the age of 39 due to neck discomfort and left-sided THA was demonstrated. Affected individuals were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Kit) and all identified variants were evaluated for pathogenicity. Sanger sequencing was used to confirm WES data and check segregation among first-degree relatives. RESULTS: In both siblings, a compound heterozygous mutations NM_000168.6: c.[2179G>A];[4039C>A] (NP_000159.3: p.[Gly727Arg];[Gln1347Lys]) were identified in the GLI3 gene, affecting exon 14 and 15, respectively. According to the American College of Medical Genetics, variants are classified as of uncertain significance, and were found to be very rare (GnomAD MAF 0.007131 and 0.00003187). The segregation mapping and analysis of relatives indicated causativeness of compound heterozygosity. CONCLUSIONS: We demonstrated for the first time a unique association of THA phenotype and the presence of compound heterozygous mutations p.[Gly727Arg];[Gln1347Lys] of GLI3 gene in two siblings. Springer US 2020-07-21 2021 /pmc/articles/PMC7881956/ /pubmed/32696176 http://dx.doi.org/10.1007/s12020-020-02422-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Endocrine Genetics/Epigenetics Szczepanek-Parulska, Ewelina Budny, Bartłomiej Borowczyk, Martyna Zawadzka, Katarzyna Sztromwasser, Paweł Ruchała, Marek Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis |
title | Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis |
title_full | Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis |
title_fullStr | Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis |
title_full_unstemmed | Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis |
title_short | Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis |
title_sort | compound heterozygous gli3 variants in siblings with thyroid hemiagenesis |
topic | Endocrine Genetics/Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881956/ https://www.ncbi.nlm.nih.gov/pubmed/32696176 http://dx.doi.org/10.1007/s12020-020-02422-1 |
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