Abstract
Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC) is a rare disease and since the first report, it has been found in just over 200 families approximately, around the world (Smit et al. in Clin Genet 79:49–59, 2009). Patients in Colombia or in Latin America have not been described, as far as we know. HLRCC is inherited in an autosomal dominant manner, and it is caused by heterozygous germline mutations in the FH gene, which encodes the fumarate hydratase enzyme. It is characterized mainly by the appearance of cutaneous and uterine leiomyomas, and an early-onset, aggressive form of type 2- papillary renal cell carcinoma (Smit et al. in Clin Genet 79:49–59, 2009; Schmidt and Linehan in Int J Nephrol Renovasc Dis 7:253–260, 2014]. We report a Colombian family with HLRCC syndrome, with a novel mutation in FH gene (c.1349_1352delATGA) in which cutaneous leiomyomas have not been found, but other clinical manifestations such as type 2- papillary renal cell carcinoma, uterine leiomyomas and rare tumors were present. This investigation constitutes the first report of HLRCC syndrome in Colombia, and probably in Latin America.
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Abbreviations
- HLRCC:
-
Hereditary leiomyomatosis and renal cell cancer
- NRF2 :
-
Factor erythroid 2-related factor 2
- AMPK :
-
AMP-activated protein kinase
- PCR:
-
Polymerase chain reaction
- PHD:
-
Prolyl hydroxylases
- HIF-1a :
-
Hypoxia inducible factor 1 alpha
- 2SC:
-
2 Succinyl-cysteine
- CT:
-
Computed tomography
- WT:
-
Wild Type sequence
- GLUT1 :
-
Glucose transporter 1
- VEGF :
-
Vascular endothelial growth factor
- KEAP 1 :
-
Kelchlike ECH associated protein 1
- ROS:
-
Reactive oxygen species
- GISTs:
-
Gastrointestinal stromal tumors
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Acknowledgments
The authors would like to thank the patients for their willingness to participate. We are grateful to Jorge Eduardo Caminos Pinzon, PhD in neuroendocrinology and member of the Department of Physiological Sciences at the Faculty of Medicine, Universidad Nacional de Colombia, for kindly letting us use one of his genetics labs, and for all his assistance. Also to Maria Fernanda Garces Gutierrez, MSc Human Genetics and PhD student of Biotechnology, Universidad Nacional de Colombia for all her help in the lab. Finally, we want to thank Alvaro Sierra, who helped us with the blood extraction.
Authors’ contribution
CAV and CAD conceived the study, participated in its design and coordination, and in writing the manuscript. CAV, CAD, MRL, collected clinical data. CAV, CAD, EGR interpreted all clinical data. ACB and CAV participated in the genetic analysis. All authors read and approved the final manuscript.
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Arenas Valencia, C., Rodríguez López, M.L., Cardona Barreto, A.Y. et al. Hereditary leiomyomatosis and renal cell cancer syndrome: identification and clinical characterization of a novel mutation in the FH gene in a Colombian family. Familial Cancer 16, 117–122 (2017). https://doi.org/10.1007/s10689-016-9922-4
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DOI: https://doi.org/10.1007/s10689-016-9922-4