oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Molecular and clinical genetic studies of a novel variant of familial hypercalcemia
Uppsala universitet, Institutionen för kirurgiska vetenskaper, Uppsala, Sweden.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Familial primary hyperparathyroidism (HPT) is a rare disorder that is treated surgically and mostly occurs in association with tumor-susceptibility syndromes, like multiple endocrine neoplasia and the hyperparathyroidism-jaw tumor syndrome. Familial hypercalciuric hypercalcemia (FHH) is another cause of hereditary hypercalcemia that generally is considered to require no treatment and is genetically and pathophysiologically distinct from HPT. Inactivating mutations in the calcium receptor gene cause FHH, whereas the down-regulated expression of the CaR in HPT never has been coupled to CaR gene mutations.

Family screening revealed a hitherto unknown familial condition with characteristics of both FHH and HPT. The hypercalcemia was mapped to a point mutation in the intracellular domain of the CaR gene that was coupled to relative calcium resistance of the PTH release by transient expression in HEK 294 cells. Unusually radical excision of parathyroid glands was required to normalise the hypercalcemia. The mildly enlarged parathyroid glands displayed hyperplasia with nodular components. Frequent allelic loss on especially 12q was found and contrasts to findings in HPT. Allelic loss was also seen in loci typical for primary HPT like 1p, 6q and 15q, but not 11q13. Quantitative mRNA analysis showed that the glands had mild increase in a proliferation index (PCNA/GAPDH mRNA ratio) and mild reduction in genes important to parathyroid cell function, like CaR, PTH, VDR and LRP2.

A previously unrecognized variant of hypercalcemia is explored that could be one explanation for persistent hypercalcemia after apparently typical routine operations for HPT. It also raises the issue of possibilities to treat FHH with parathyroidectomy provided it is radical enough.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2002. , 56 p.
Keyword [en]
Surgery, hyperparathyroidism, calcium receptor, hypercalcemia, allelic loss, autosomal inheritance
Keyword [sv]
Kirurgi
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:oru:diva-57632ISBN: 91-554-5300-7 (print)OAI: oai:DiVA.org:oru-57632DiVA: diva2:1094822
Public defence
2002-05-16, Hedstrandssalen, Ing 70 bv, Akademiska sjukhuset, 13:15
Opponent
Available from: 2017-05-26 Created: 2017-05-11 Last updated: 2017-05-26Bibliographically approved

Open Access in DiVA

fulltext(373 kB)8 downloads
File information
File name FULLTEXT01.pdfFile size 373 kBChecksum SHA-512
07553ebdb099b56eacf842e6cbca4d9e7f3e962d9a44e07aed642681cec815a8512c7fb75b625a6ddafc4f10812a6c863a8944155c9567e9c2f64721aeeb2332
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Szabo, Eva
Surgery

Search outside of DiVA

GoogleGoogle Scholar
Total: 8 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 14 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf