Penetrance and clinical features of pheochromocytoma in a six-generation family carrying a germline TMEM127 mutation.

J Clin Endocrinol Metab

Divisions of Endocrinology (S.P.A.T., D.M.L.J., T.S.), Urology (A.M.L.), Hypertension and Radiology (M.E.S.B., C.C.C., L.A.B.), and Pathology (M.C.N.Z., S.A.C.S.), University of São Paulo School of Medicine, Hospital das Clínicas and Heart Institute (INCOR), São Paulo 01246-903, Brazil; and Division of Hematology and Oncology, Department of Medicine, Cancer Therapy and Research Center (R.A.T., P.L.M.D.), Greehey Childhood Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.

Published: February 2015

AI Article Synopsis

  • The study investigates the characteristics and penetrance of pheochromocytoma (PHEO) related to TMEM127 mutations in a six-generation family, where 151 individuals were screened for the mutation.
  • Results showed that 32% of mutation carriers developed PHEO, with symptoms often starting at a young age; tumors were found to be multicentric and bilateral in many cases.
  • The findings emphasize the importance of genetic testing for at-risk relatives due to the high penetrance of pheochromocytoma, and introduce new insights into the age of onset and tumor characteristics in TMEM127-related PHEO.

Article Abstract

Context: The phenotype of familial pheochromocytoma (PHEO) associated with germline TMEM127 mutations (TMEM127-related PHEO) has not been clearly defined.

Objective: This study aimed to investigate the penetrance, full phenotypic spectrum and effectiveness of clinical/genetic screening in TMEM127-related PHEO.

Design, Setting, And Participants: Clinical and genetic screening, and genetic counseling were offered to 151 individuals from a six-generation family carrying a TMEM127 germline mutation in a referral center.

Intervention And Main Outcome Measures: TMEM127 genetic testing was offered to at-risk relatives and clinical surveillance for pheochromocytoma was performed in mutation-positive carriers.

Results: Forty seven individuals carried the c.410-2A>C TMEM127 mutation. Clinical data were obtained from 34 TMEM127-mutation carriers followed up for 8.7 ± 8.1 years (range, 1-20 y). Pheochromocytoma was diagnosed in 11 carriers (32%) at a median age of 43 years. In nine patients, symptoms started at 29 years (range, 10-55 y) and two cases were asymptomatic. Tumors were multicentric in five (45%) and bilateral in five (45%) patients. Six patients (54%) had at least one adrenomedullary nodule less than 10 mm. No paragangliomas, distant metastases, or other manifestations were detected. Cumulative penetrance of pheochromocytoma was 0% at 0-20 years, 3% at 21-30 years, 15% at 31-40 years, 24% at 41-50 years, and 32% at 51-65 years. The youngest case was diagnosed at 22 years and the earliest symptoms were reported at age 10.

Conclusions: Tumor multicentricity, nodular adrenomedullary hyperplasia, and the occurrence of symptoms more than a decade earlier than the age at diagnosis are novel findings in TMEM127-related PHEO. The high penetrance of pheochromocytoma in this condition validates the benefits of genetic testing of at-risk relatives. We thus recommend that TMEM127 genetic testing should be offered to at-risk individuals at age 22 years and mutation carriers should undergo clinical surveillance annually.

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2014-2473DOI Listing

Publication Analysis

Top Keywords

genetic testing
12
years
10
six-generation family
8
family carrying
8
germline tmem127
8
tmem127 mutation
8
tmem127-related pheo
8
tmem127 genetic
8
testing offered
8
offered at-risk
8

Similar Publications

Adaptive radiations are rich laboratories for exploring, testing, and understanding key theories in evolution and ecology because they offer spectacular displays of speciation and ecological adaptation. Particular challenges to the study of adaptive radiation include high levels of species richness, rapid speciation, and gene flow between species. Over the last decade, high-throughput sequencing technologies and access to population genomic data have lessened these challenges by enabling the analysis of samples from many individual organisms at whole-genome scales.

View Article and Find Full Text PDF

Objectives: To delineate and understand the genetic variations among strains from Trinidad and Tobago associated with gastric diseases.

Methods: One hundred (n = 100) patients who routinely presented with clinical features suggestive of peptic disease were enrolled in the study and underwent gastroscopy procedures. Biopsy specimens were analyzed using serological and molecular methods.

View Article and Find Full Text PDF

Hereditary dentine disorders are autosomal dominant diseases that affect the development and structure of dentine, leading to various dental abnormalities and influencing the individual's oral health. It is generally classified as dentinogenesis imperfecta (DGI) and dentine dysplasia (DD). Specifically, DGI is characterized by the abnormal formation of dentine, resulting in teeth that are discolored, translucent, and prone to fracture or wear down easily.

View Article and Find Full Text PDF

Background: Cancer patients frequently suffer from pain, often managed with opioids. However, undertreated pain remains a significant concern. Opioid effectiveness varies due to genetic differences in how individuals metabolize some of these medications.

View Article and Find Full Text PDF

Background And Objective: The role of genetic variants in response to systemic therapy in muscle-invasive bladder cancer (MIBC) is still elusive. We assessed variations in genes involved in DNA damage repair (DDR) before and after cisplatin-based neoadjuvant chemotherapy (NAC) and correlation of alteration patterns with DNA damage and response to therapy.

Methods: Matched tissue from 46 patients with MIBC was investigated via Ion Torrent-based next-generation sequencing using a self-designed panel of 30 DDR genes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: