Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes
ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with...
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| Format: | Article |
| Language: | English |
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Brazilian Society of Endocrinology and Metabolism
2023-11-01
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| Series: | Archives of Endocrinology and Metabolism |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972024000100303&tlng=en |
| _version_ | 1797542641723768832 |
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| author | Tarık Kırkgöz Semra Gürsoy Sezer Acar Özlem Nalbantoğlu Beyhan Özkaya Hüseyin Anıl Korkmaz Filiz Hazan Behzat Özkan |
| author_facet | Tarık Kırkgöz Semra Gürsoy Sezer Acar Özlem Nalbantoğlu Beyhan Özkaya Hüseyin Anıl Korkmaz Filiz Hazan Behzat Özkan |
| author_sort | Tarık Kırkgöz |
| collection | DOAJ |
| description | ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH. |
| first_indexed | 2024-03-10T13:34:25Z |
| format | Article |
| id | doaj.art-f2799dd056dd4cfeaa2ad6a847e0e2b8 |
| institution | Directory Open Access Journal |
| issn | 2359-4292 |
| language | English |
| last_indexed | 2024-03-10T13:34:25Z |
| publishDate | 2023-11-01 |
| publisher | Brazilian Society of Endocrinology and Metabolism |
| record_format | Article |
| series | Archives of Endocrinology and Metabolism |
| spelling | doaj.art-f2799dd056dd4cfeaa2ad6a847e0e2b82023-11-21T07:43:22ZengBrazilian Society of Endocrinology and MetabolismArchives of Endocrinology and Metabolism2359-42922023-11-016810.20945/2359-4292-2022-0254Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genesTarık Kırkgözhttps://orcid.org/0000-0003-3450-9780Semra Gürsoyhttps://orcid.org/0000-0002-6795-3012Sezer Acarhttps://orcid.org/0000-0002-0768-835XÖzlem Nalbantoğluhttps://orcid.org/0000-0002-0410-5761Beyhan Özkayahttps://orcid.org/0000-0002-4161-2631Hüseyin Anıl Korkmazhttps://orcid.org/0000-0001-5800-9014Filiz Hazanhttps://orcid.org/0000-0002-0382-3446Behzat Özkanhttps://orcid.org/0000-0002-9153-8409ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972024000100303&tlng=enPituitaryHypopituitarismisolated growth hormone deficiencycombined pituitary hormone deficiencyGLI2PROP1LHX4POU1F1 |
| spellingShingle | Tarık Kırkgöz Semra Gürsoy Sezer Acar Özlem Nalbantoğlu Beyhan Özkaya Hüseyin Anıl Korkmaz Filiz Hazan Behzat Özkan Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes Archives of Endocrinology and Metabolism Pituitary Hypopituitarism isolated growth hormone deficiency combined pituitary hormone deficiency GLI2 PROP1 LHX4 POU1F1 |
| title | Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes |
| title_full | Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes |
| title_fullStr | Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes |
| title_full_unstemmed | Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes |
| title_short | Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes |
| title_sort | genetic diagnosis of congenital hypopituitarism in turkish patients by a target gene panel novel pathogenic variants in ghrhr gli2 lhx4 and pou1f1 genes |
| topic | Pituitary Hypopituitarism isolated growth hormone deficiency combined pituitary hormone deficiency GLI2 PROP1 LHX4 POU1F1 |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972024000100303&tlng=en |
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