Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency
Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identific...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/16/5757 |
| _version_ | 1797558863214411776 |
|---|---|
| author | Bartłomiej Budny Katarzyna Karmelita-Katulska Marek Stajgis Tomasz Żemojtel Marek Ruchała Katarzyna Ziemnicka |
| author_facet | Bartłomiej Budny Katarzyna Karmelita-Katulska Marek Stajgis Tomasz Żemojtel Marek Ruchała Katarzyna Ziemnicka |
| author_sort | Bartłomiej Budny |
| collection | DOAJ |
| description | Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely <i>LHX4, HESX1</i>, and <i>OTX2</i>. Among new CPHD loci, the most interesting seem to be the region covering <i>SIX3</i> gene, that is abundantly expressed in developing brain, and together with <i>HESX1</i> contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology. |
| first_indexed | 2024-03-10T17:37:21Z |
| format | Article |
| id | doaj.art-44351a642c6448d19468d85c3043ba65 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:37:21Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-44351a642c6448d19468d85c3043ba652023-11-20T09:48:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116575710.3390/ijms21165757Copy Number Variants Contributing to Combined Pituitary Hormone DeficiencyBartłomiej Budny0Katarzyna Karmelita-Katulska1Marek Stajgis2Tomasz Żemojtel3Marek Ruchała4Katarzyna Ziemnicka5Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of General Radiology and Neuroradiology, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of General Radiology and Neuroradiology, Poznan University of Medical Sciences, 60-355 Poznan, PolandGenomics Platform, Berlin Institute of Health, 10117 Berlin, GermanyDepartment of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandCombined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely <i>LHX4, HESX1</i>, and <i>OTX2</i>. Among new CPHD loci, the most interesting seem to be the region covering <i>SIX3</i> gene, that is abundantly expressed in developing brain, and together with <i>HESX1</i> contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology.https://www.mdpi.com/1422-0067/21/16/5757CPHDCNVsmicroarrays |
| spellingShingle | Bartłomiej Budny Katarzyna Karmelita-Katulska Marek Stajgis Tomasz Żemojtel Marek Ruchała Katarzyna Ziemnicka Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency International Journal of Molecular Sciences CPHD CNVs microarrays |
| title | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
| title_full | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
| title_fullStr | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
| title_full_unstemmed | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
| title_short | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
| title_sort | copy number variants contributing to combined pituitary hormone deficiency |
| topic | CPHD CNVs microarrays |
| url | https://www.mdpi.com/1422-0067/21/16/5757 |
| work_keys_str_mv | AT bartłomiejbudny copynumbervariantscontributingtocombinedpituitaryhormonedeficiency AT katarzynakarmelitakatulska copynumbervariantscontributingtocombinedpituitaryhormonedeficiency AT marekstajgis copynumbervariantscontributingtocombinedpituitaryhormonedeficiency AT tomaszzemojtel copynumbervariantscontributingtocombinedpituitaryhormonedeficiency AT marekruchała copynumbervariantscontributingtocombinedpituitaryhormonedeficiency AT katarzynaziemnicka copynumbervariantscontributingtocombinedpituitaryhormonedeficiency |