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HRPT2-related familial isolated hyperparathyroidism: could molecular studies direct the surgical approach?
Leticia G Silveira1, Eduardo P Dias, Bruna C G Marinho
1Departamentos de Farmácia, Belo Horizonte, MG, Brasil.
Abstract:
It is still debatable which is the best management to familial forms of hyperparathyroidism. Conservative, minimally invasive or aggressive surgical approaches have been proposed from different groups around the world. Our objective was to study the gene mutation, expression of HRPT2 and the clinical outcome after 32 years of follow-up in one Brazilian kindred with familial isolated hyperparathyroidism (FIHP). Clinical and biochemical data, direct sequencing of the HRPT2 gene, analysis of parafibromin expression using RT-PCR, and immunohistochemistry were done. A nonsense mutation was found in exon 1 (c.96G>A)(p.Trp32X) in all affected members studied. Using RT-PCR, mRNA transcription was altered with complete absence of both transcripts in tumor tissue. Immunohistochemical analysis of tumors showed loss of parafibromin immunoreactivity. In this kindred there was a high prevalence of recurrence (75%), or persistence after less than subtotal parathyroidectomy that led us to consider a more aggressive surgical approach should be discussed among the affected family members, once surgical criteria was met. We concluded that it is necessary to individualize the surgical approach for HRPT2-related hyperparathyroidism until we can gather a better phenotype-genotype correlation in larger series, to best define their treatment.
Insights
Familial isolated hyperparathyroidism (FIHP) linked to HRPT2 gene mutations often recurs. Personalized, potentially aggressive surgical management is crucial for managing this genetic endocrine disorder.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Familial isolated hyperparathyroidism (FIHP) management remains debated.
- Surgical approaches vary globally, lacking a consensus for familial hyperparathyroidism.
- Understanding genetic mutations and clinical outcomes is vital for treatment strategies.
Observation:
- A Brazilian kindred with FIHP was studied over 32 years.
- Genetic analysis identified a nonsense mutation (c.96G>A)(p.Trp32X) in the HRPT2 gene in affected members.
- Tumor tissue showed altered mRNA transcription and loss of parafibromin expression.
Findings:
- The HRPT2 mutation led to a high recurrence rate (75%) or persistence of hyperparathyroidism post-parathyroidectomy.
- Loss of parafibromin, a tumor suppressor, was observed in affected parathyroid tissues.
- The identified mutation significantly impacts clinical outcomes in this FIHP kindred.
Implications:
- Results suggest a need for individualized surgical approaches in HRPT2-related hyperparathyroidism.
- A more aggressive surgical strategy may be warranted for affected families.
- Further research on phenotype-genotype correlations is needed to optimize treatment for FIHP.
