Thoughts on the results of genetic map of a family (A25)

Introduction: Neuroendocrine tumors associated with MEN1-4 genetic syndrome are more and more
recognized. The evolving understanding of genotype-phenotypic relationships and disease progression
is changing the way we manage patients.

Aim(s): For typical patients whose gene testing results are negative, the scope and depth of gene test can be expanded.

Materials and methods: Collected and tested blood samples of the patient’s mother, mother’s brother and sister and their next generation, the patient and her brother and their next generation.

Results: The patient, a 47-year-old female, underwent left parathyroidectomy for parathyroid tumor in 2013. Pancreatic tumor resection was performed in 2021, confirmed PNET. No germline mutant gene was found at that time. Fatigue appeared in 2022, PTH 235.54pg/mL, bilateral parathyroidectomy was performed. Her brother was diagnosed with Adult Still Syndrome in 2007 and lung metastasis of renal clear cell carcinoma in 2021; mother lung cancer at the age of 40; niece pituitary adenoma at the age of 16. Blood samples collected, germline testing carried out in 2023, 6/11 were detected MEN1 mutation (c.35C>T) interpreted as likely-pathogenic. Her 18-year-old twin sons, one of whom has the pathogenic mutation, and the other is negative. The sequence change replaces proline with leucine at codon 12 of MEN1 protein (p. Pro12Leu). Proline residues are highly conserved, while there are moderate physical and chemical differences between proline and leucine, which may affect the function of MEN1.

Conclusion: For typical clinical features and clear family history, if results of the first gene test are negative, further expanded gene testing can be done. Genetic counseling for patients and conduct clinical and genetic screening of patients’ first-degree relatives.

Keywords: family, germline mutant, men1