Familial isolated primary hyperparathyroidism/hyperparathyroidism‐jaw tumour syndrome caused by germline gross deletion or point mutations of CDC73 gene in Chinese. (6th May 2014)

• Record Type: Journal Article
• Authors: Kong, Jing; Wang, Ou; Nie, Min; Shi, Jie; Hu, Yingying; Jiang, Yan; Li, Mei; Xia, Weibo; Meng, Xunwu; Xing, Xiaoping
• Is Part Of: Clinical endocrinology. Volume 81:Number 2(2014:Aug.)
• Page Start: 222
• Page End: 230
• Publication Date: 2014-05-06
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12461
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12461-abs-0001"> <title>Summary</title> <sec id="cen12461-sec-0001" sec-type="section"> <title>Objective</title> <p>Hyperparathyroidism‐jaw tumour syndrome (HPT‐JT) and familial isolated primary hyperparathyroidism (FIHP) are two subtypes of familial primary hyperparathyroidism, which are rarely reported in Chinese population. Here, we reported three FIHP families and one HPT‐JT family with long‐term follow‐up and genetic analysis.</p> </sec> <sec id="cen12461-sec-0002" sec-type="section"> <title>Design and methods</title> <p>A total of 22 patients, from four FIHP/HPT‐JT families of Chinese descent, were recruited and genomic DNA was extracted from their peripheral blood lymphocytes. Direct sequencing for <italic>MEN1</italic>, <italic> CDC73, CASR</italic> gene was conducted. Reverse transcription PCR (RT–PCR) and quantitative real‐time PCR (qRT‐PCR) were used to study the effect of splice site mutations and gross deletion mutations. Immunohistochemistry was performed to analyse parafibromin expression in parathyroid tumours. Genotype–phenotype correlations were assessed through clinical characteristics and long‐term follow‐up data.</p> </sec> <sec id="cen12461-sec-0003" sec-type="section"> <title>Results</title> <p>Genetic analysis revealed four <italic>CDC73</italic> germline mutations that were responsible for the four kindreds, including two novel point mutation (c.157 G>T and IVS3+1 G>A), one recurrent point mutation (c.664 C>T) and one deletion mutation (c.307+?_513‐?del exons 4, 5, 6). RT‐PCR confirmed that IVS3+1 G>A generated an aberrant transcript with exon3 deletion. Immunohistochemical analysis demonstrated reduced nuclear parafibromin expression in tumours supporting the pathogenic effects of these mutations.</p> </sec> <sec id="cen12461-sec-0004" sec-type="section"> <title>Conclusions</title> <p>This study supplies information on mutations and phenotypes of HPT‐JT/FIHP syndrome in Chinese. Screening for gross deletion and point mutations of the <italic>CDC73</italic> gene is necessary in susceptible subjects.</p> </sec> </abstract>