A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing
Background: Primary macronodular adrenocortical hyperplasia (PMAH) is a rare form of adrenal Cushing’s syndrome with incomplete penetrance which may be sporadic or autosomal dominant. The inactivation of the <i>ARMC5</i> gene, a potential tumor suppressor gene, is one of the associated c...
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MDPI AG
2022-12-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/12/3028 |
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| author | Maryam Eghbali Sara Cheraghi Sara Samanian Iman Rad Jafar Meghdadi Hamideh Akbari Maryam Honardoost |
| author_facet | Maryam Eghbali Sara Cheraghi Sara Samanian Iman Rad Jafar Meghdadi Hamideh Akbari Maryam Honardoost |
| author_sort | Maryam Eghbali |
| collection | DOAJ |
| description | Background: Primary macronodular adrenocortical hyperplasia (PMAH) is a rare form of adrenal Cushing’s syndrome with incomplete penetrance which may be sporadic or autosomal dominant. The inactivation of the <i>ARMC5</i> gene, a potential tumor suppressor gene, is one of the associated causes of PMAH. This study aimed to identify the variant responsible for Iranian familial PMAH. Methods: The proband, a 44-year-old woman, was directed to whole-exome sequencing (WES) of the blood sample to discover a germline variant. In addition, the identified causative variant was confirmed and segregated in other and available unaffected family members. Results: The novel germline heterozygous missense variant, c.2105C>A in the <i>ARMC5</i> gene, was found, and the same germline variant as the proband was confirmed in two affected sisters. This variant was detected in the brother of the proband with an asymptomatic condition and this considered because of incomplete penetrance and age-dependent appearance. The function of the <i>ARMC5</i> protein would be damaged by the identified variant, according to in silico and computer analyses that followed. Conclusion: The new germline <i>ARMC5</i> variation (c.2105C>A, (p. Ala702Glu)) was interpreted as a likely pathogenic variant based on ACMG and Sherloc standards. PMAH may be diagnosed early using genetic testing that shows inherited autosomal dominant mutations in the <i>ARMC5</i> gene. |
| first_indexed | 2024-03-09T17:08:10Z |
| format | Article |
| id | doaj.art-357f0e9efdef480d80402954be332488 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T17:08:10Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-357f0e9efdef480d80402954be3324882023-11-24T14:17:23ZengMDPI AGDiagnostics2075-44182022-12-011212302810.3390/diagnostics12123028A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome SequencingMaryam Eghbali0Sara Cheraghi1Sara Samanian2Iman Rad3Jafar Meghdadi4Hamideh Akbari5Maryam Honardoost6Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran 1593716615, IranEndocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran 1593716615, IranGenetic Foundation of Tehran, Solaleh Diagnostic Laboratory, Tehran 1393845944, IranStem Cell Technology Research Center (STRC), Tehran 1665666311, IranStem Cell Technology Research Center (STRC), Tehran 1665666311, IranClinical Research Development Unit (CRDU), Sayad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan 49178677439, IranEndocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran 1593716615, IranBackground: Primary macronodular adrenocortical hyperplasia (PMAH) is a rare form of adrenal Cushing’s syndrome with incomplete penetrance which may be sporadic or autosomal dominant. The inactivation of the <i>ARMC5</i> gene, a potential tumor suppressor gene, is one of the associated causes of PMAH. This study aimed to identify the variant responsible for Iranian familial PMAH. Methods: The proband, a 44-year-old woman, was directed to whole-exome sequencing (WES) of the blood sample to discover a germline variant. In addition, the identified causative variant was confirmed and segregated in other and available unaffected family members. Results: The novel germline heterozygous missense variant, c.2105C>A in the <i>ARMC5</i> gene, was found, and the same germline variant as the proband was confirmed in two affected sisters. This variant was detected in the brother of the proband with an asymptomatic condition and this considered because of incomplete penetrance and age-dependent appearance. The function of the <i>ARMC5</i> protein would be damaged by the identified variant, according to in silico and computer analyses that followed. Conclusion: The new germline <i>ARMC5</i> variation (c.2105C>A, (p. Ala702Glu)) was interpreted as a likely pathogenic variant based on ACMG and Sherloc standards. PMAH may be diagnosed early using genetic testing that shows inherited autosomal dominant mutations in the <i>ARMC5</i> gene.https://www.mdpi.com/2075-4418/12/12/3028PMAHwhole-exome sequencing<i>ARMC5</i>novel germline variant |
| spellingShingle | Maryam Eghbali Sara Cheraghi Sara Samanian Iman Rad Jafar Meghdadi Hamideh Akbari Maryam Honardoost A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing Diagnostics PMAH whole-exome sequencing <i>ARMC5</i> novel germline variant |
| title | A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing |
| title_full | A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing |
| title_fullStr | A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing |
| title_full_unstemmed | A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing |
| title_short | A Novel <i>ARMC5</i> Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing |
| title_sort | novel i armc5 i germline variant in primary macronodular adrenal hyperplasia using whole exome sequencing |
| topic | PMAH whole-exome sequencing <i>ARMC5</i> novel germline variant |
| url | https://www.mdpi.com/2075-4418/12/12/3028 |
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