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RESEARCH PRODUCT
Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization
Consol López San MartinEnrique LastraMercedes RobledoJosé María Mesa-latorreGemma LlortMaría FonfriaLuis GómezJudith BalmañaA Beatriz Sánchez-herasAdela CastillejoAlexandre TeuléPere BerbelTeresa Ramón Y CajalJuan De Dios García-díazÁNgel ZúñigaMercedes DuránAdrià López-fernándezIsabel ChirivellaM. Isabel CastillejoLuis RoblesInés EscandellRaquel Perea IbañezCarmen YagüeRosario SánchezJosé Luis Sotosubject
0301 basic medicineOncologyCancer ResearchCancer cellsmedicine.disease_causeurologic and male genital diseases:Male Urogenital Diseases::Urogenital Neoplasms::Urologic Neoplasms::Kidney Neoplasms::Male Urogenital Diseases::Carcinoma Renal Cell [DISEASES]<i>FH</i> gene0302 clinical medicineMalalties hereditàriesMissense mutationFH geneFH gene hereditary leiomyomatosis leiomyomas missense pathogenic variants renal cell cancerRenal cell cancerMutationKidney diseasesHereditary leiomyomatosis:Otros calificadores::Otros calificadores::/genética [Otros calificadores]:enfermedades urogenitales masculinas::neoplasias urogenitales::neoplasias urológicas::neoplasias renales::enfermedades urogenitales masculinas::carcinoma de células renales [ENFERMEDADES]leiomyomasmissense pathogenic variants renal cell cancerlcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensRare diseases:Geographic Locations::Europe::Spain [GEOGRAPHICALS]Oncology030220 oncology & carcinogenesisCohortCèl·lules cancerosesMalalties raresRenal Cell CancersGenetic disordersmedicine.medical_specialtyMissense pathogenic variantsBiología Celularlcsh:RC254-282Article03 medical and health sciencesLeiomyomasInternal medicine:Other subheadings::Other subheadings::/genetics [Other subheadings]medicineRonyons - Malalties - Espanya:localizaciones geográficas::Europa (continente)::España [DENOMINACIONES GEOGRÁFICAS]business.industry:neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido muscular::leiomioma::leiomiomatosis [ENFERMEDADES]Retrospective cohort studymedicine.diseaseGenética030104 developmental biologyFumaraseClinical diagnosisHereditary leiomyomatosis and renal cell cancer syndromeMalalties del ronyó:Neoplasms::Neoplasms by Histologic Type::Neoplasms Connective and Soft Tissue::Neoplasms Muscle Tissue::Leiomyoma::Leiomyomatosis [DISEASES]hereditary leiomyomatosisbusinessdescription
Simple Summary Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancer (RCC), with no data on its prevalence worldwide. No genotype-phenotype associations have been described. The aim of our study was to describe the genotypic and phenotypic features of the largest series of patients with HLRCC from Spain reported to date. Of 27 FH germline pathogenic variants, 12 were not previously reported in databases. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants. The frequency of RCCs (10.9%) was lower than those reported in the previously published series. Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-11-05 |