One genotype, many phenotypes: SDHB p.R90X mutation-associated paragangliomas
Ali S Alzahrani1,2, Meshael Alswailem3, Yosra Moria4
1Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. aliz@kfshrc.edu.sa.
Context:
SDHB p.R90X germline mutation is the most common genetic alteration in our patients with familial or apparently sporadic pheochromocytoma/paraganglioma (PPGL).
Objective:
To analyze the clinical and pathological characteristics, response to therapy, and outcome of patients with SDHB p.R90X-associated PPGL and describe the clinical phenotypic variability in the patients carrying this mutation.
Methods:
We reviewed the clinical and pathological characteristics and analyzed the phenotypic variability of all 13 patients that have SDHB p.R90X mutation-associated PPGL.
Results:
Thirteen patients (five females and eight males). The median age at diagnosis was 23 years (range 8-43). Although the mutation was the same, there was significant phenotypic variability between patients and even within the same family. Four patients (30.8%) had a family history of PPGL and six patients (46%) had distant metastasis. Surgery of the primary tumor was performed in 11 patients (84.6%). Two patients had inoperable PPGL. Patients with metastasis received different combinations of chemotherapy, Lu177 radiotherapy, multikinase inhibitors, and external irradiation. Only five patients (38.5%) were in remission at a follow-up duration of 4-9 years. The other patients either died due to their disease progression (four patients, 30.8%) or continue to have progressive disease (two patients, 15.4%) or recurrence (one patient, 7.7%). Patients with distant metastasis were older, had larger primary tumors, were more likely to have a family history of PPGL and had a worse outcome.
Conclusion:
SDHB p.R90X mutation-associated PPGL have significant phenotypic variability and are associated with a high risk of distant metastasis and mortality.
Insights
The SDHB p.R90X mutation, common in pheochromocytoma/paraganglioma (PPGL), shows significant variability. This mutation is linked to a high risk of metastasis and mortality in affected patients.
Area of Science:
- Endocrinology
- Oncology
- Genetics
Background:
- The SDHB p.R90X germline mutation is a frequent genetic driver in pheochromocytoma/paraganglioma (PPGL).
- Understanding the clinical spectrum of this mutation is crucial for patient management.
Purpose of the Study:
- To investigate the clinical and pathological features of PPGL associated with the SDHB p.R90X mutation.
- To analyze treatment responses and outcomes.
- To describe the phenotypic variability in patients with this mutation.
Main Methods:
- Retrospective review of clinical and pathological data.
- Analysis of phenotypic variability in 13 patients with SDHB p.R90X-associated PPGL.
Main Results:
- Significant phenotypic variability observed, even within families.
- High rates of distant metastasis (46%) and a family history of PPGL (30.8%).
- Poor outcomes, with 38.5% in remission after 4-9 years, and significant mortality (30.8%).
Conclusions:
- SDHB p.R90X-associated PPGL exhibits considerable phenotypic diversity.
- This mutation confers a substantial risk of distant metastasis and mortality.
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