title: SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations.
abstract: OBJECTIVE
  Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma (PHEO/PGL). Limited information is available concerning PHEO/PGL penetrance among SDHB mutation carriers with regards to primary tumor location, specific mutation type, and gender. We assessed PHEO/PGL penetrance in SDHB mutation carriers and described the clinical presentation and disease course.
  
  
  METHODS
  Asymptomatic relatives (N = 611) of 103 index patients were tested for SDHB mutations. Mutation carriers (N = 328) were offered PHEO/PGL screening, of which 241 participated and were included in penetrance analysis. For additional disease outcome analysis, the 103 index patients and 40 screened individuals who developed PHEO/PGL were included. Clinical data were collected between October 2004 and June 2016.
  
  
  RESULTS
  Forty (16.60%) of the 241 screened individuals developed PHEO/PGL during the study. The penetrance estimate in this population was 49.80% (95% CI 29-74.9) at 85 years. A significantly higher age-related penetrance of disease was observed in males compared to females, with 50% penetrance achieved at age 74 vs. not reached. Age-related penetrance analysis demonstrated 4 mutations (Ile127Ser, IVS1+1G>T, Exon 1 deletion, Arg90X) presenting with a slower rate of disease development (50% penetrance ages, respectively: not achieved, 70, 63, 61 years) compared to Arg46X and Val140Phe mutations (50% penetrance at 38 years).
  
  
  CONCLUSIONS
  Here, we found a higher estimated penetrance compared to several other studies, and a striking difference in age-related penetrance between male and female SDHB mutation carriers with no association between mutation and gender or tumor location.
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA.|1st Department of Internal Medicine, Medical Faculty of P. J. Šafárik University in Košice, Trieda SNP 1, 04011, Košice, Slovakia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jochmanova
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA.
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Wolf
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: King
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Nambuba
authors.affiliation: Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wesley
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Martucci
authors.affiliation: Section on Developmental Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Raygada
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Adams
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Prodanov
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Antonio Tito
authors.initials: AT
authors.lastname: Fojo
authors.affiliation: 1st Department of Internal Medicine, Medical Faculty of P. J. Šafárik University in Košice, Trieda SNP 1, 04011, Košice, Slovakia.
authors.forename: Ivica
authors.initials: I
authors.lastname: Lazurova
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA. karel@mail.nih.gov.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D019683:Penetrance; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: C108095:SDHB protein, human; D013385:Succinate Dehydrogenase
keywords: Paraganglioma; Penetrance; Pheochromocytoma; SDHB; Sex differences