Endocrine Abstracts

Germline activating mutations of the RET proto-oncogene are associated with inherited medullary thyroid cancer (MTC) and can be also detected in about 10% of apparently sporadic MTC cases. In the present study, 4 novel RET mutations, located in the extracellular domain (A510V, E511K and C531R) and in the intracellular juxtamembrane region (L666N), all identified by the genetic screening on sporadic MTC cases, are firstly reported and functionally characterized. RET Plasmids ca...

Multiple endocrine neoplasia type 1 (MEN1) is a rare dominantly inherited neoplastic syndrome. Tipically, it affects three major locations: parathyroid, endocrine pancreas or duodenum (GEP) and anterior pituitary. MEN1 is caused by mutations in MEN1 gene and its testing is now used as a complement to clinical diagnosis which may be hindered by the variable penetrance and expression of the defects. Mutation carriers are life-long monitored, while unaffected relatives can avoid ...

Activating mutations of the RET proto-oncogene, encoding a tyrosine kinase receptor, are associated with inherited syndromes, MEN2A and MEN2B, and with both familial and sporadic medullary thyroid cancer (MTC). Single base-pair missense mutations in the extracellular cysteine-rich domain are responsible for the majority of MEN2A and familial MTC (FMTC) cases. Rarely, somatic deletions and germline duplications of variable segments of the gene have been reported in spora...

Primary ovarian insufficiency (POI) is a heterogeneous disorder characterized by primary (PA) or secondary (SA) amenorrhea associated with increased levels of gonadotropins. POI affects about 1% of women before the age of 40 years. A major genetic component has been suggested for idiopathic POI due to the frequent familiarity for this defect. Indeed, FMR1 premutations can be found in 10–15% and BMP15 mutations in 2–5% of POI patients. Numerous other candidate genes h...

Many single nucleotide polymorphisms (SNPs) of the RET gene have been described both in the general population and in patients with sporadic medullary thyroid cancer (sMTC), MEN2 or Hirschsprung disease. Some association studies reported a higher prevalence of these variants in the affected patients, suggesting a possible role in modifying the risk of occurrence of the disease. However, data from different cohorts of sMTC are discrepant and the aim of the present study ...

Mild hypothyroidism is a heterogeneous and frequent disorder in the general population that is due to autoimmune disease in most of the cases. TSH resistance is considered a rare genetic disease due to germline loss-of-function TSHR mutations. However, TSHR mutations have been mainly searched in patients with large TSH elevations and their actual prevalence among patients with mild TSH elevations (as those found in mild hypothyroidism) is so far unknown. In this study, we eval...