A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia
Background/Objective: Familial hypocalciuric hypercalcemia (FHH) is an uncommon cause of hypercalcemia; however, it is important to consider and rule out in patients with suspected primary hyperparathyroidism (PHPT), ideally, before proceeding with surgery. Herein, we present a patient where this pr...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | AACE Clinical Case Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2376060522000372 |
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| author | Panagiotis Bletsis, MD Rosemarie Metzger, MD J. Alex Nelson, DO Justin Gasparini, MS Mahmoud Alsayed, MD Mira Milas, MD |
| author_facet | Panagiotis Bletsis, MD Rosemarie Metzger, MD J. Alex Nelson, DO Justin Gasparini, MS Mahmoud Alsayed, MD Mira Milas, MD |
| author_sort | Panagiotis Bletsis, MD |
| collection | DOAJ |
| description | Background/Objective: Familial hypocalciuric hypercalcemia (FHH) is an uncommon cause of hypercalcemia; however, it is important to consider and rule out in patients with suspected primary hyperparathyroidism (PHPT), ideally, before proceeding with surgery. Herein, we present a patient where this process identified a calcium-sensing receptor gene (CASR) sequence variant currently labeled as a variant of unknown significance (VUS), yet the patient’s family pedigree suggests that it is in fact a pathogenic CASR sequence variant. Case Report: A 35-year-old woman was referred to the Endocrine Surgery clinic for evaluation of “recurrent PHPT” and need for reoperative parathyroidectomy. Before referral, she was treated with subtotal parathyroidectomy for the presumed diagnosis of PHPT-related symptomatic hypercalcemia. Postoperatively, she had persistent symptoms. Upon referral, additional relevant information was elicited that suspected FHH instead of PHPT, including a family history of hypercalcemia with CASR VUS in multiple family members and hypocalciuria in the patient. She underwent genetic testing revealing a missense CASR VUS in exon 3 c.392C>A (p.Ala110Asp), the same as in her mother. Medical management instead of reoperation was advised for the diagnosis of FHH. Discussion: To our knowledge, this CASR sequence variation has not been previously reported in the literature. Reporting newly discovered sequence variations with the context of a family’s medical history is important because it allows for the recognition of new pathogenic variants. This expands the registry of already known sequence variations and their associated clinical pathology for future patients undergoing genetic testing. Conclusion: This CASR variant represents a novel pathogenic sequence variation causing FHH. |
| first_indexed | 2024-04-12T19:02:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2376-0605 |
| language | English |
| last_indexed | 2024-04-12T19:02:17Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | AACE Clinical Case Reports |
| spelling | doaj.art-886a689676c945c09c4ce769ac5f205f2022-12-22T03:20:07ZengElsevierAACE Clinical Case Reports2376-06052022-09-0185194198A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric HypercalcemiaPanagiotis Bletsis, MD0Rosemarie Metzger, MD1J. Alex Nelson, DO2Justin Gasparini, MS3Mahmoud Alsayed, MD4Mira Milas, MD5Division of Endocrine Surgery, Department of Surgery, Banner University Medical Center Phoenix/University of Arizona College of Medicine PhoenixDivision of Endocrine Surgery, Department of Surgery, Banner University Medical Center Phoenix/University of Arizona College of Medicine PhoenixDivision of Endocrine Surgery, Department of Surgery, Banner University Medical Center Phoenix/University of Arizona College of Medicine PhoenixDivision of Endocrine Surgery, Department of Surgery, Banner University Medical Center Phoenix/University of Arizona College of Medicine Phoenix; Department of Clinical Cancer Genetics, Banner MD Anderson Cancer Center Phoenix; Division of Endocrinology, Department of Internal Medicine, Banner University Medical Center Phoenix/University of Arizona College of Medicine PhoenixDivision of Endocrinology, Department of Internal Medicine, Banner University Medical Center Phoenix/University of Arizona College of Medicine PhoenixDivision of Endocrine Surgery, Department of Surgery, Banner University Medical Center Phoenix/University of Arizona College of Medicine PhoenixBackground/Objective: Familial hypocalciuric hypercalcemia (FHH) is an uncommon cause of hypercalcemia; however, it is important to consider and rule out in patients with suspected primary hyperparathyroidism (PHPT), ideally, before proceeding with surgery. Herein, we present a patient where this process identified a calcium-sensing receptor gene (CASR) sequence variant currently labeled as a variant of unknown significance (VUS), yet the patient’s family pedigree suggests that it is in fact a pathogenic CASR sequence variant. Case Report: A 35-year-old woman was referred to the Endocrine Surgery clinic for evaluation of “recurrent PHPT” and need for reoperative parathyroidectomy. Before referral, she was treated with subtotal parathyroidectomy for the presumed diagnosis of PHPT-related symptomatic hypercalcemia. Postoperatively, she had persistent symptoms. Upon referral, additional relevant information was elicited that suspected FHH instead of PHPT, including a family history of hypercalcemia with CASR VUS in multiple family members and hypocalciuria in the patient. She underwent genetic testing revealing a missense CASR VUS in exon 3 c.392C>A (p.Ala110Asp), the same as in her mother. Medical management instead of reoperation was advised for the diagnosis of FHH. Discussion: To our knowledge, this CASR sequence variation has not been previously reported in the literature. Reporting newly discovered sequence variations with the context of a family’s medical history is important because it allows for the recognition of new pathogenic variants. This expands the registry of already known sequence variations and their associated clinical pathology for future patients undergoing genetic testing. Conclusion: This CASR variant represents a novel pathogenic sequence variation causing FHH.http://www.sciencedirect.com/science/article/pii/S2376060522000372familial hypocalciuric hypercalcemia (FHH)primary hyperparathyroidism (PHPT)genetic testingSherloc classification system |
| spellingShingle | Panagiotis Bletsis, MD Rosemarie Metzger, MD J. Alex Nelson, DO Justin Gasparini, MS Mahmoud Alsayed, MD Mira Milas, MD A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia AACE Clinical Case Reports familial hypocalciuric hypercalcemia (FHH) primary hyperparathyroidism (PHPT) genetic testing Sherloc classification system |
| title | A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia |
| title_full | A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia |
| title_fullStr | A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia |
| title_full_unstemmed | A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia |
| title_short | A Novel Missense CASR Gene Sequence Variation Resulting in Familial Hypocalciuric Hypercalcemia |
| title_sort | novel missense casr gene sequence variation resulting in familial hypocalciuric hypercalcemia |
| topic | familial hypocalciuric hypercalcemia (FHH) primary hyperparathyroidism (PHPT) genetic testing Sherloc classification system |
| url | http://www.sciencedirect.com/science/article/pii/S2376060522000372 |
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