PMID- 32761341
OWN - NLM
STAT- MEDLINE
DCOM- 20210825
LR  - 20211002
IS  - 1868-8500 (Electronic)
IS  - 1868-8497 (Print)
IS  - 1868-8497 (Linking)
VI  - 11
IP  - 5-6
DP  - 2020 Oct
TI  - Outcome of Clinical Genetic Testing in Patients with Features Suggestive for 
      Hereditary Predisposition to PTH-Mediated Hypercalcemia.
PG  - 250-255
LID - 10.1007/s12672-020-00394-2 [doi]
AB  - Primary hyperparathyroidism (pHPT) is associated with familial syndromes such as 
      multiple endocrine neoplasia type 1 (MEN1), 2A (MEN2A), MEN-like syndromes 
      (CDKN1B), and CDC73-related disorder (hyperparathyroidism - jaw tumor syndrome 
      (HPJT)). Familial hypocalciuric hypercalcemia (FHH) caused by CASR variants is an 
      important differential diagnosis for pHPT. In order to evaluate the contribution 
      of hereditary causes to pHPT in patients encountered in a specialized clinic, we 
      conducted a retrospective study on patients with pHPT that underwent germline 
      genetic testing. We evaluated 46 patients referred to a Cancer Genetics Clinic. 
      Reasons for referral were young age (age < 40) for 29 patients (63%), multi-gland 
      disease for 23 patients (50%), and a positive family history of pHPT for 11 
      patients (24%). All 46 patients underwent genetic evaluation. A total of 11 rare 
      variants were found (CASR (4), CDC73 (2), MEN1 (2) CDKN1B (1), and RET (2)). One 
      MEN1 variant was classified as pathogenic, and all others were variants of 
      uncertain significance (VUS). All patients with CASR variants had clinical 
      features of FHH and were counselled against parathyroidectomy. Both patients with 
      CDC73 variants were counselled about recurrence of pHPT and parathyroid cancer. 
      Neither of the RET variants were MEN2-associated. The CDKN1B variant was regarded 
      as a true VUS and no action was taken. In this study, genetic testing impacted 
      clinical care in 7 (15%) patients. We suggest that all patients < 40 years of 
      age, with multi-gland disease, single gland disease refractory to treatment, and 
      a positive family history for pHPT or associated tumors should be considered for 
      genetic evaluation.
FAU - Khairi, Shafaq
AU  - Khairi S
AD  - Department of Internal Medicine, Division of Metabolism, Endocrinology and 
      Diabetes, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI, 
      48109, USA.
FAU - Osborne, Jenae
AU  - Osborne J
AD  - Department of Internal Medicine, Division of Genetic Medicine, University of 
      Michigan, Ann Arbor, MI, USA.
FAU - Jacobs, Michelle F
AU  - Jacobs MF
AD  - Department of Internal Medicine, Division of Genetic Medicine, University of 
      Michigan, Ann Arbor, MI, USA.
FAU - Clines, Gregory T
AU  - Clines GT
AD  - Department of Internal Medicine, Division of Metabolism, Endocrinology and 
      Diabetes, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI, 
      48109, USA.
FAU - Miller, Barbra S
AU  - Miller BS
AD  - Department of Surgery, Division of Endocrine Surgery, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Hughes, David T
AU  - Hughes DT
AD  - Department of Surgery, Division of Endocrine Surgery, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Else, Tobias
AU  - Else T
AUID- ORCID: 0000-0002-2262-0011
AD  - Department of Internal Medicine, Division of Metabolism, Endocrinology and 
      Diabetes, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI, 
      48109, USA. telse@umich.edu.
LA  - eng
GR  - T32 DK007245/DK/NIDDK NIH HHS/United States
GR  - T32DK007245/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200805
PL  - United States
TA  - Horm Cancer
JT  - Hormones & cancer
JID - 101518427
SB  - IM
MH  - Adult
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genetic Testing/*methods
MH  - Humans
MH  - Hypercalcemia/*congenital
MH  - Hyperparathyroidism, Primary/*genetics
MH  - Treatment Outcome
PMC - PMC7945006
MID - NIHMS1672446
OTO - NOTNLM
OT  - Familial hypocalciuric hypercalcemia
OT  - Genetic predisposition syndromes
OT  - Germline variants
OT  - Primary hyperparathyroidism
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/08/08 06:00
MHDA- 2021/08/26 06:00
PMCR- 2020/08/05
CRDT- 2020/08/08 06:00
PHST- 2020/05/13 00:00 [received]
PHST- 2020/07/27 00:00 [accepted]
PHST- 2020/08/08 06:00 [pubmed]
PHST- 2021/08/26 06:00 [medline]
PHST- 2020/08/08 06:00 [entrez]
PHST- 2020/08/05 00:00 [pmc-release]
AID - 10.1007/s12672-020-00394-2 [pii]
AID - 394 [pii]
AID - 10.1007/s12672-020-00394-2 [doi]
PST - ppublish
SO  - Horm Cancer. 2020 Oct;11(5-6):250-255. doi: 10.1007/s12672-020-00394-2. Epub 2020 
      Aug 5.