CDC73 intragenic deletion in familial primary hyperparathyroidism associated with parathyroid carcinoma.
BACKGROUND
CDC73 mutations frequently underlie the hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma. It has also been suggested that CDC73 deletion analysis should be performed in those patients without CDC73 mutations.


OBJECTIVE
To investigate for CDC73 deletion in a family with FIHP previously reported not to have CDC73 mutations.


METHODS
Eleven members (six affected with primary hyperparathyroidism and five unaffected) were ascertained from the family, and multiplex ligation-dependent probe amplification was performed to detect CDC73 deletion using leukocyte DNA.


RESULTS
A previously unreported deletion of CDC73 involving exons 1-10 was detected in five affected members and two unaffected members who were 26 and 39 years of age. Two affected members had parathyroid carcinomas at the ages of 18 and 32 years, and they had Ki-67 proliferation indices of 5 and 14.5% and did not express parafibromin, encoded by CDC73. Primary hyperparathyroidism in the other affected members was due to adenomas and atypical adenomas, and none had jaw tumors. Two affected members had thoracic aortic aneurysms, which in one member occurred with parathyroid carcinoma and renal cysts.


CONCLUSIONS
A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas. In addition, two affected males had thoracic aortic aneurysms, which may represent another associated clinical feature of this disorder.
Department of Internal Medicine, Seinäjoki Central Hospital (E.K.-H.), 60320 Seinäjoki, Finland; Oxford Medical Genetics Laboratory, Churchill Hospital (T.C.), Division of Endocrinology, Department of Medicine (E.R., T.S., C.S-J.), Department of Pathology (J.A.), and Department of Medical Genetics (K.A), Helsinki University Central Hospital, FI-00290 Helsinki, Finland; and Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford (R.V.T.), Oxford OX1 2JD, United Kingdom.
Eeva
E
Korpi-Hyövälti
Treena
T
Cranston
Eeva
E
Ryhänen
Johanna
J
Arola
Kristiina
K
Aittomäki
Timo
T
Sane
Rajesh V
RV
Thakker
Camilla
C
Schalin-Jäntti
D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D005192:Family Health; D005260:Female; D005350:Fibroma / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D007573:Jaw Neoplasms / Q000235:genetics*; D008297:Male; D010282:Parathyroid Neoplasms / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins