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Familial isolated primary hyperparathyroidism/hyperparathyroidism‐jaw tumour syndrome caused by germline gross deletion or point mutations of CDC 73 gene in Chinese
Author(s) -
Kong Jing,
Wang Ou,
Nie Min,
Shi Jie,
Hu Yingying,
Jiang Yan,
Li Mei,
Xia Weibo,
Meng Xunwu,
Xing Xiaoping
Publication year - 2014
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12461
Subject(s) - primary hyperparathyroidism , point mutation , exon , germline mutation , mutation , genetics , microbiology and biotechnology , biology , gene mutation , gene , immunohistochemistry , hyperparathyroidism , endocrinology , immunology
Summary Objective 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. Design and methods 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 MEN1 , CDC73, CASR 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. Results Genetic analysis revealed four CDC 73 germline mutations that were responsible for the four kindreds, including two novel point mutation (c.157 G>T and IVS 3+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 IVS 3+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. Conclusions This study supplies information on mutations and phenotypes of HPT ‐ JT / FIHP syndrome in Chinese. Screening for gross deletion and point mutations of the CDC 73 gene is necessary in susceptible subjects.