Affordable Access

Access to the full text

Whole exome sequencing in familial isolated primary hyperparathyroidism

Authors
  • Cetani, F.1
  • Pardi, E.2
  • Aretini, P.3
  • Saponaro, F.2
  • Borsari, S.2
  • Mazoni, L.2
  • Apicella, M.2
  • Civita, P.3
  • La Ferla, M.3
  • Caligo, M. A.4
  • Lessi, F.3
  • Mazzanti, C. M.3
  • Torregossa, L.4
  • Oppo, A.5
  • Marcocci, C.2
  • 1 University Hospital of Pisa, Endocrine Unit 2, Via Paradisa 2, Pisa, 56124, Italy , Pisa (Italy)
  • 2 University of Pisa, Pisa, Italy , Pisa (Italy)
  • 3 Fondazione Pisana per la Scienza ONLUS, Pisa, Italy , Pisa (Italy)
  • 4 University Hospital of Pisa, Pisa, Italy , Pisa (Italy)
  • 5 University of Cagliari, Cagliari, Italy , Cagliari (Italy)
Type
Published Article
Journal
Journal of Endocrinological Investigation
Publisher
Springer-Verlag
Publication Date
Sep 05, 2019
Volume
43
Issue
2
Pages
231–245
Identifiers
DOI: 10.1007/s40618-019-01107-5
Source
Springer Nature
Keywords
License
Yellow

Abstract

PurposeFamilial isolated hyperparathyroidism (FIHP) is a rare inherited disease accounting for 1% of all cases of primary hyperparathyroidism (PHPT). It is genetically heterogeneous being associated with mutations in different genes, including MEN1, CDC73, CASR, and recently GCM2. The aim of the study was to further investigate the molecular pathogenesis in Italian FIHP kindreds.MethodsWe used whole exome sequencing (WES) in the probands of seven unrelated FIHP kindreds. We carried out a separate family-based exome analysis in a large family characterized by the co-occurrence of PHPT with multiple tumors apparently unrelated to the disease. Selected variants were also screened in 18 additional FIHP kindreds. The clinical, biochemical, and pathological characteristics of the families were also investigated.ResultsThree different variants in GCM2 gene were found in two families, but only one (p.Tyr394Ser), already been shown to be pathogenic in vitro, segregated with the disease. Six probands carried seven heterozygous missense mutations segregating with the disease in the FAT3, PARK2, HDAC4, ITPR2 and TBCE genes. A genetic variant in the APC gene co-segregating with PHPT (p.Val530Ala) was detected in a family whose affected relatives had additional tumors, including colonic polyposis.ConclusionWe confirm the role of GCM2 germline mutations in the pathogenesis of FIHP, although at a lower rate than in the previous WES study. Further studies are needed to establish the prevalence and the role in the predisposition to FIHP of the novel variants in additional genes.

Report this publication

Statistics

Seen <100 times