The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants
Familial glucocorticoid deficiency is a rare autosomal recessive genetic disorder which belongs to a group of primary adrenal insufficiency (PAI) and is mainly caused by mutations in the MC2R and MRAP genes. A comprehensive search was conducted to find the reported variants of MC2R and MRAP genes. I...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2020/2190508 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552547450093568 |
|---|---|
| author | Katayoun Heshmatzad Nejat Mahdieh Ali Rabbani Abdolah Didban Bahareh Rabbani |
| author_facet | Katayoun Heshmatzad Nejat Mahdieh Ali Rabbani Abdolah Didban Bahareh Rabbani |
| author_sort | Katayoun Heshmatzad |
| collection | DOAJ |
| description | Familial glucocorticoid deficiency is a rare autosomal recessive genetic disorder which belongs to a group of primary adrenal insufficiency (PAI) and is mainly caused by mutations in the MC2R and MRAP genes. A comprehensive search was conducted to find the reported variants of MC2R and MRAP genes. In silico pathogenic analysis was performed for the reported variants. PCR amplification and sequencing were performed for three patients. Structural analysis, modeling, and interactome analysis were applied to characterize novel MC2R variants and their proteins. About 80% of MC2R-related cases showed the clinical symptoms which were diagnosed at <2 years old. 107 patients had MC2R mutations (85 homozygotes, 21 compound heterozygotes, and 1 simple heterozygote). 59 variants were found in the MC2R gene. Four mutations were responsible for half of patients. 39 homozygous patients had MRAP mutations; 14 variants were determined in the MRAP gene. Nine proteins were predicted by STRING to associate with the studied proteins. Two novel MC2R variants, c.128T > G (p.Leu43Arg) and c.251T > A (p.Ile84Asn), were found in two patients at the age of above and below 2 years, respectively. Mutations in MC2R and MRAP genes are the main cause of FGD. Genetic studies and in silico analysis will help to confirm the diagnosis. |
| format | Article |
| id | doaj-art-14886c4dd4194be68c7cdc78900ddc87 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-14886c4dd4194be68c7cdc78900ddc872025-02-03T05:58:22ZengWileyInternational Journal of Endocrinology1687-83371687-83452020-01-01202010.1155/2020/21905082190508The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel VariantsKatayoun Heshmatzad0Nejat Mahdieh1Ali Rabbani2Abdolah Didban3Bahareh Rabbani4Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, IranGrowth and Development Research Center, Tehran University of Medical Sciences, Tehran, IranGrowth and Development Research Center, Tehran University of Medical Sciences, Tehran, IranDepartment of Pediatrics, Pediatric Endocrinologist, Qazvin University of Medical Sciences, Qazvin, IranGrowth and Development Research Center, Tehran University of Medical Sciences, Tehran, IranFamilial glucocorticoid deficiency is a rare autosomal recessive genetic disorder which belongs to a group of primary adrenal insufficiency (PAI) and is mainly caused by mutations in the MC2R and MRAP genes. A comprehensive search was conducted to find the reported variants of MC2R and MRAP genes. In silico pathogenic analysis was performed for the reported variants. PCR amplification and sequencing were performed for three patients. Structural analysis, modeling, and interactome analysis were applied to characterize novel MC2R variants and their proteins. About 80% of MC2R-related cases showed the clinical symptoms which were diagnosed at <2 years old. 107 patients had MC2R mutations (85 homozygotes, 21 compound heterozygotes, and 1 simple heterozygote). 59 variants were found in the MC2R gene. Four mutations were responsible for half of patients. 39 homozygous patients had MRAP mutations; 14 variants were determined in the MRAP gene. Nine proteins were predicted by STRING to associate with the studied proteins. Two novel MC2R variants, c.128T > G (p.Leu43Arg) and c.251T > A (p.Ile84Asn), were found in two patients at the age of above and below 2 years, respectively. Mutations in MC2R and MRAP genes are the main cause of FGD. Genetic studies and in silico analysis will help to confirm the diagnosis.http://dx.doi.org/10.1155/2020/2190508 |
| spellingShingle | Katayoun Heshmatzad Nejat Mahdieh Ali Rabbani Abdolah Didban Bahareh Rabbani The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants International Journal of Endocrinology |
| title | The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants |
| title_full | The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants |
| title_fullStr | The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants |
| title_full_unstemmed | The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants |
| title_short | The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants |
| title_sort | genetic perspective of familial glucocorticoid deficiency in silico analysis of two novel variants |
| url | http://dx.doi.org/10.1155/2020/2190508 |
| work_keys_str_mv | AT katayounheshmatzad thegeneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT nejatmahdieh thegeneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT alirabbani thegeneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT abdolahdidban thegeneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT baharehrabbani thegeneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT katayounheshmatzad geneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT nejatmahdieh geneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT alirabbani geneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT abdolahdidban geneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants AT baharehrabbani geneticperspectiveoffamilialglucocorticoiddeficiencyinsilicoanalysisoftwonovelvariants |