Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation.

BACKGROUND: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome. CASE PRESENTATION: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.Gly225Aspfs*56 in exon 4 of the MEN1 gene. Diagnosis and clinical phenotyping of MEN1 was established by laboratory tests, ultrasound, biopsy, MRI imaging and endosonography. The clinical course of the disease was followed in the index patient and her family members for eight years. The mutation was associated with distinct clinical phenotypes in the index patient and three family members harboring p.Gly225Aspfs*56. Family members affected showed primary hyperparathyroidism but variable patterns of associated endocrine tumors, adrenal cortical adenomas, prolactinoma, multifocal pancreatic neuroendocrine tumors, insulinoma and nonsecretory neuroendocrine tumors of the pancreas. The mutation c.674delG; p.Gly225Aspfs*56 leads to a frameshift from codon 225 with early truncation of the menin protein. In silico analysis predicts loss of multiple protein-menin interactions in p.Gly225Aspfs*56, potentially rendering menin insufficient to control cell division and replication. However, no aggressive neuroendocrine tumors were observed in the follow-up of this family. CONCLUSIONS: We report a novel heterozygous MEN1 frameshift mutation, potentially causing (at least partial) inactivation of menin tumor suppression potential but lacking a genotype-phenotype correlation. Our study highlights the importance of personalized care with appropriate testing and counseling in MEN1 families.

[Patient blood management--The preoperative patient]. / Patient Blood Management--Der präoperative Patient.

Preoperative anaemia is an independent risk factor for an increase in perioperative morbidity and mortality. Patient Blood Management (PBM) aims for an early detection of anaemia in elective surgery patients. Reasons for anaemia should be detected and causally treated if possible. A multidisciplinary team of specialists aims for diagnosis and causative treatment of easily treatable and frequent causes of anaemia like iron deficiency, bleeding or (autoimmune) haemolysis using patients' specific history, examination, laboratory and technical methods. Such an outpatient PBM programme is only feasible, if anaesthesiologists, surgeons, haematologists, gastroenterologists, gynecologists, laboratory and transfusion medicine specialists work together in a PBM team using a common PBM plan. Communication within this team as well as with the patients' physicians in their private offices is key for a long lasting success of such a PBM programme.