How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase
Objective: To describe a case of a personal and family history of early uterine leiomyomatosis that revealed a pathogenic variant in the FH gene encoding fumarate hydratase. After the patient’s diagnosis, a first-degree relative was detected with early-stage renal cell carcinoma. The patient decided...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | F&S Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666334121001185 |
| _version_ | 1818285219202990080 |
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| author | Greysha Rivera-Cruz, M.D. Baris Boyraz, M.D., Ph.D. John C. Petrozza, M.D. |
| author_facet | Greysha Rivera-Cruz, M.D. Baris Boyraz, M.D., Ph.D. John C. Petrozza, M.D. |
| author_sort | Greysha Rivera-Cruz, M.D. |
| collection | DOAJ |
| description | Objective: To describe a case of a personal and family history of early uterine leiomyomatosis that revealed a pathogenic variant in the FH gene encoding fumarate hydratase. After the patient’s diagnosis, a first-degree relative was detected with early-stage renal cell carcinoma. The patient decided to undergo preimplantation genetic testing to reduce the risk to her future children. Design: A case report of autosomal dominant hereditary leiomyomatosis and renal cell cancer syndrome where the patient underwent 2 cycles of in vitro fertilization with preimplantation genetic testing for monogenic disease/aneuploidy (PGT-MA) that resulted in 3 unaffected, euploid embryos. Setting: Large academic single-center hospital. Patient(s): A 35-year-old nulligravida woman with a personal history of an early-onset uterine leiomyomatosis and a family history of renal cell carcinoma and uterine leiomyomas, who is heterozygous for a pathogenic variant in FH and diagnosed with hereditary leiomyomatosis and renal cell cancer syndrome. Informed consent was obtained. Intervention(s): Two laparoscopic myomectomies were performed, and tissue was sent for histopathology and immunostaining. Hereditary leiomyomatosis and renal cell cancer syndrome was confirmed by germline testing, and 2 cycles of PGT-MA were performed. Main Outcome Measure(s): Through PGT-MA, the patient was able to mitigate the risk of passing a known familial variant to her future children. Result(s): After 2 cycles of in vitro fertilization with PGT-MA, 3 unaffected embryos were available for transfer. An unaffected, euploid embryo was transferred for pregnancy, and the patient is currently pregnant in her second trimester. Conclusion(s): Pathogenic variants in FH should be suspected in patients with early-onset uterine leiomyomas and a family history of cutaneous and/or uterine leiomyomas. Familial variant testing is crucial in identifying relatives at risk to start early screening. |
| first_indexed | 2024-12-13T01:05:13Z |
| format | Article |
| id | doaj.art-79c5f3826dc4401593f37a06a9e73cc1 |
| institution | Directory Open Access Journal |
| issn | 2666-3341 |
| language | English |
| last_indexed | 2024-12-13T01:05:13Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | F&S Reports |
| spelling | doaj.art-79c5f3826dc4401593f37a06a9e73cc12022-12-22T00:04:34ZengElsevierF&S Reports2666-33412022-03-01312631How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydrataseGreysha Rivera-Cruz, M.D.0Baris Boyraz, M.D., Ph.D.1John C. Petrozza, M.D.2Division of Genetics and Genomics, Harvard Medical School, Boston Children’s Hospital, Boston, Massachusetts; Reprint requests: Greysha Rivera-Cruz, M.D., Division of Genetics and Genomics, Harvard Medical School, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115.Department of Pathology, Massachusetts General Hospital, Boston, MassachusettsDivision of Reproductive Medicine and In vitro Fertilization, Massachusetts General Fertility Center, Boston, MassachusettsObjective: To describe a case of a personal and family history of early uterine leiomyomatosis that revealed a pathogenic variant in the FH gene encoding fumarate hydratase. After the patient’s diagnosis, a first-degree relative was detected with early-stage renal cell carcinoma. The patient decided to undergo preimplantation genetic testing to reduce the risk to her future children. Design: A case report of autosomal dominant hereditary leiomyomatosis and renal cell cancer syndrome where the patient underwent 2 cycles of in vitro fertilization with preimplantation genetic testing for monogenic disease/aneuploidy (PGT-MA) that resulted in 3 unaffected, euploid embryos. Setting: Large academic single-center hospital. Patient(s): A 35-year-old nulligravida woman with a personal history of an early-onset uterine leiomyomatosis and a family history of renal cell carcinoma and uterine leiomyomas, who is heterozygous for a pathogenic variant in FH and diagnosed with hereditary leiomyomatosis and renal cell cancer syndrome. Informed consent was obtained. Intervention(s): Two laparoscopic myomectomies were performed, and tissue was sent for histopathology and immunostaining. Hereditary leiomyomatosis and renal cell cancer syndrome was confirmed by germline testing, and 2 cycles of PGT-MA were performed. Main Outcome Measure(s): Through PGT-MA, the patient was able to mitigate the risk of passing a known familial variant to her future children. Result(s): After 2 cycles of in vitro fertilization with PGT-MA, 3 unaffected embryos were available for transfer. An unaffected, euploid embryo was transferred for pregnancy, and the patient is currently pregnant in her second trimester. Conclusion(s): Pathogenic variants in FH should be suspected in patients with early-onset uterine leiomyomas and a family history of cutaneous and/or uterine leiomyomas. Familial variant testing is crucial in identifying relatives at risk to start early screening.http://www.sciencedirect.com/science/article/pii/S2666334121001185Fumarate hydrataseuterine leiomyomarenal cell carcinomapreimplantation genetic testing |
| spellingShingle | Greysha Rivera-Cruz, M.D. Baris Boyraz, M.D., Ph.D. John C. Petrozza, M.D. How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase F&S Reports Fumarate hydratase uterine leiomyoma renal cell carcinoma preimplantation genetic testing |
| title | How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase |
| title_full | How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase |
| title_fullStr | How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase |
| title_full_unstemmed | How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase |
| title_short | How a woman’s myomectomy saved her father’s life: evidence of fumarate hydratase–deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase |
| title_sort | how a woman s myomectomy saved her father s life evidence of fumarate hydratase deficient uterine leiomyoma and early detection of germline variants in fumarate hydratase |
| topic | Fumarate hydratase uterine leiomyoma renal cell carcinoma preimplantation genetic testing |
| url | http://www.sciencedirect.com/science/article/pii/S2666334121001185 |
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