Mutations Of CDC73 Gene Research Articles

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

BackgroundPrimary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor.Case presentationThe proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband’s daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient’s blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father’s first signs of brown tumor were in the right maxilla, while the daughter’s appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland.ConclusionWe report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

Parathyroid carcinoma during pregnancy: a novel pathogenic CDC73 mutation – a case report

BackgroundParathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcemia. Only a handful of cases have been reported of parathyroid carcinoma during pregnancy.Case presentationTwenty-four – Year – old female presented with proximal myopathy was found to have hypercalcemia. Her serum corrected total calcium was – 15 mg/dl (8.5 – 10.3), serum phosphate – 2.3 mg/dl (2.5 – 4.5), intact PTH – 118 pg/ml (20 – 80), Vitamin D – 15 ng/ml and Urine Ca/Cr ratio – 2.1 (0.1 – 0.2). Her CECT–neck revealed a well-defined mass lesion posterior to the right lobe of the thyroid – 2.6 cm × 2.5 cm × 2.9 cm in size. She was started on vitamin D supplementation, and she underwent right lower focal parathyroidectomy. Her PTH levels normalized following surgery. Her histology revealed an atypical parathyroid adenoma. She was treated with calcium and vitamin D. Her follow up was uneventful.One year following initial surgery the patient became pregnant and at 16 weeks of POA, the patient presented with a rapidly enhancing neck mass for one week duration. Her biochemical investigations were suggestive of a recurrence of primary hyperparathyroidism. Her ultrasound scan of the neck revealed a well-defined discreate hypoechoic nodule, superior to the thyroid isthmus which was confirmed by a non-contrast MRI scan of the neck. She underwent an uncomplicated second trimester parathyroid tumour excision with normalization of post op PTH. Her histology revealed a parathyroid carcinoma with vascular and capsular invasion. Her genetic studies revealed a novel frameshift mutation of the CDC73 gene. She was treated with calcium and vitamin D supplementation and closely followed up with ionized calcium and PTH levels which were normal throughout the pregnancy. She had an uncomplicated caesarean section at a POA of 37 weeks. Currently she is twelve weeks post-partum, in remission of disease.ConclusionThis case shows the importance of stringent follow up of atypical parathyroid adenoma patients, the benefit of second trimester surgery in management of hypercalcemia due to parathyroid carcinoma during pregnancy and the importance of identifying the novel CDC73 gene mutation.

Patterns and Predictors of Cervical Lymph Node Metastasis in Parathyroid Carcinoma.

Simple SummaryParathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Surgery remains the mainstay of PC treatment. However, due to the rarity of this malignancy, the optimal extent of PC surgery remains inconclusive, including whether to perform central lymph node dissection (LND). In the present study, we reported the patterns and predictors of cervical lymph node metastasis in PC based on a cohort of 68 PC patients. The results showed that the percentage of cervical lymph node metastasis in PC was 19.4% at initial surgery and 25.0% including reoperations for recurrencies. High-risk Schulte staging and CDC73 abnormalities were identified as risk factors for cervical lymph node metastasis. Central LND should be considered during remedial surgeries performed after previous local resection of PC for patients with high risk factors.Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Over 60% of PC patients experience repeated disease recurrence or metastasis. The significance of cervical lymph node dissection (LND) for PC remains inconclusive. Methods: PC patients diagnosed at Peking Union Medical College Hospital between 1992 and 2021 were reviewed retrospectively. Clinical data, initial tumor histological staging, parafibromin histochemical staining results, Ki67 index, CDC73 gene mutation status and outcome information were collected systemically. The risk factors for recurrence and lymph node or distant metastasis were explored. Results: Sixty-eight PC patients receiving LND were enrolled. Cervical lymph node metastasis was identified in 19.4% of patients at initial surgery and 25.0% of patients including reoperations for recurrences. The independent risk factor for PC recurrence was a Ki67 index ≥ 5% (HR4.41, 95% confidence interval (CI)1.30–14.95, p = 0.017). Distant metastasis was an independent prognostic factor for PC patient overall survival (HR 5.44, 95% CI 1.66–17.82, p = 0.005). High-risk Schulte staging (p = 0.021) and CDC73 abnormalities (p = 0.012) were risk factors for cervical lymph node metastasis. Conclusion: Most PCs were slow-growing, but lymph node metastasis was not rare. For patients planning to undergo remedial surgery after previous local resection of PC, central LND is suggested for tumors with high-risk Schulte staging or CDC73 abnormalities.

In silico analysis of CDC73 gene revealing 11 novel SNPs with possible association to Hyperparathyroidism-Jaw Tumor syndrome

Abstract Hyperparathyroidism-Jaw Tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the most deleterious SNPs mutations on CDC73 gene and to predict their influence on the functional and structural levels using different bioinformatics tools. Method: Computational analysis using twelve different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, P-Mut, I-Mutant ,Project Hope, Chimera, COSMIC and dbSNP Short Genetic Variations were used to identify the impact of mutations in CDC73 gene that might be causing jaw tumor. Results: From (733) SNPs identified in the CDC73 gene we found that only Eleven SNPs (G49C, L63P, L64P, D90H, R222G, W231R, P360S, R441C, R441H, R504S and R504H) has deleterious effect on the function and structure of protein and expected to cause the syndrome. Conclusion: Eleven substantial genetic/molecular aberrations in CDC73 gene identified that could serve as diagnostic markers for hyperparathyroidism-jaw tumor (HPT-JT).

289O - Spectrum of mitochondrial genomic variation in parathyroid neoplasms by ultra-deep targeted DNA sequencing

BackgroundParathyroid neoplasms are characterized with hypersecretion of parathyroid hormone and potentially exhibit disruption of metabolic pathways. Mitochondria are essential for energy homeostasis and mitochondrial DNA (mtDNA) abnormalities are related to multiple types of malignancies. However, the status of mtDNA mutation and copy number variations in parathyroid carcinoma (PC) is not well known. MethodsUltra-deep targeted sequencing of mitochondrial genome was performed using tissues of 12 PCs and 12 parathyroid adenomas (PAs). Germline variants and somatic mutations in the mitochondrial genome were scanned and analysed in comparison with clinical features. The relative copy number of mtDNA in PCs and PAs was determined via quantitative real-time polymerase chain reaction. ResultsA total of 528 germline variants and 16 somatic mutations were identified in 24 samples of parathyroid neoplasms. All 62 non-synonymous germline variants in coding sequence (CDS) were predicted to be of low pathogenicity in PA and PC samples. Five somatic mutations with high pathogenicity in CDSs were identified in 4 (33.3%, 4/12) PC samples and 1 PA sample (8.3%, 1/12). A somatic mutation in a CDS was correlated with high mtDNA copy number in parathyroid neoplasm (p = 0.004), CDC73 gene mutation (p = 0.017) and PC recurrence (p = 0.024). More C-19 genotypes in the D310 region were found in PA than in the PC samples (3.5% vs 1.9%, p = 0.045). ConclusionsMore somatic CDS mutations with high pathogenicity were identified in PC than in PA. A high mtDNA copy number was found in parathyroid neoplasms with somatic CDS mutations and in PCs with CDC73 mutations and recurrence. Legal entity responsible for the studyThe authors. FundingThis work was supported by the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) (2017-I2M-1-001), Peking Union Medical College Innovative Team Development Program, the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32014) and the 2016 Peking Union Medical College Hospital Science Foundation for Junior Faculty (pumch-2016.2.7). DisclosureAll authors have declared no conflicts of interest.

Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is a rare endocrine malignancy, accounting for <1% of all cases of sporadic primary hyperparathyroidism (PHPT) and up to 15% in the hereditary hyperparathyroidism-jaw tumor syndrome. Genomic alterations identified in PC are mostly represented by CDC73 gene mutations, codifying for a loss-of-function protein termed parafibromin. Whole exome sequencing identified mutations in other genes, such as mTOR, KMT2D, CDKN2C, THRAP3, PIK3CA, and EZH2 genes, CCND1 gene amplification. The diagnosis of PC is quite difficult due to the lack of reliable clinical diagnostic criteria, and in the majority of cases is made postoperatively at histological examination. The clinical manifestations of PC are primarily due to the excessive secretion of PTH by the tumor rather than spread to local or distant organs. En bloc resection of the parathyroid tumor represents the initial mainstay treatment of patients with PC. Multiple surgical procedures may be required, although surgical morbidity should be taken into account. A 5- and 10-year survival between 77-100 and 49-91%, respectively, has been reported. When the tumor is no more resectable, medical treatment of hypercalcemia has a pivotal role in the management of these patients.

PO-450 Interplay between coding and non-coding genome in human parathyroid tumours

IntroductionParathyroid tumours are the second most common endocrine neoplasia in women, after thyroid cancer. Mutations in the oncosuppressor CDC73 are the key event in most carcinomas whereas alterations in the tumour suppressor MEN1 (located at 11q13.1) occur in up to a third of sporadic adenomas. Although lncRNAs play a regulatory role in endocrine cancer pathogenesis, a lncRNAs profiling in human parathyroid tumours is still missing. Here, we identified a ‘molecular signature’ able to distinguish among parathyroid histotypes and a new potential epigenetic role of MEN1 in lncRNAs regulation.Material and methodsNinety lncRNAs were investigated in 4 parathyroid carcinomas (PCas), 12 adenomas (PAds) and 2 normal glands (PaNs). Hierarchical clustering (HCL) and Significance Analysis of Microarray (SAM) were performed to identify differences in lncRNAs expression. Significant lncRNAs were validated in additional 7 PCas, 26 PAds, 6 atypical PAds (aPAds) and 4 PaNs. CDC73 and MEN1 genes mutations were detected by Sanger sequencing. PAds genomic characterisation was obtained by array Comparative Genomic Hybridization (aCGH). HEK293 cells were transiently silenced for MEN1 expression to analyse MEN1-lncRNAs correlation.Results and discussionsNine lncRNAs were identified as differentially expressed in parathyroid tissues. Specifically, KCNQ1OT1 and SNHG6 were enriched in PaNs, reduced HAR1B, MEG3, HOXA3as and NEAT1 expression characterised PAds, whereas BC200, HOXA6as and WT1-AS were upregulated in PCas. HCL identified 3 clusters in which PaNs and PCas were distinctly separated, while aPAds were closer to PCas. Moreover, PAds clustered in a highly heterogeneous way. Notably, PCas and aPAds harbouring CDC73-mutations overexpressed the majority of the lncRNAs, compared to CDC73 wild-type samples. Interestingly, BACE1-AS, KCNQ1OT1, NEAT1 and SNHG6 levels in PAds were positively correlated with MEN1 levels. aCGH analysis revealed that Chr11 loss of heterozygosity (LOH) was the main chromosomal aberration in PAds. Of note, Chr11 LOH was associated with significant HAR1B upregulation and these data were confirmed in HEK293 cells knocked-down for MEN1.ConclusionParathyroid histotypes are characterised by different lncRNAs signatures, suggesting a correlation with tumour aggressiveness and pathogenetic mechanisms. Further, our data highlight that lncRNAs profiles are related to CDC73 gene mutation status, chromosome 11 derangements and MEN1 inactivation.

Large deletion at the CDC73 gene locus and search for predictive markers of the presence of a CDC73 genetic lesion.

The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the CDC73 gene: it has been suggested that early onset of the disease and high Ca2+ levels may predict the presence of a CDC73 mutation. We searched for large deletions at the CDC73 locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a CDC73 gene mutation, clinical/histological diagnosis, age at onset, Ca2+, PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a CDC73 gene mutation. A novel genomic deletion of the first 10 exons of the CDC73 gene was found in a 3-generation HPT-JT family, confirmed by SNP array analysis. A classification tree built on the published data, showed the highest probability of having a CDC73 mutation in subjects with age at the onset < 41.5 years (44/47 subjects, 93.6%, had the mutation). Whereas the lowest probability was found in subjects with age at the onset ≥ 41.5 years and Ca2+ levels <13.96 mg/dL (7/20 subjects, 35.0%, had the mutation, odds ratio = 27.1, p < 0.001). We report a novel large genomic CDC73 gene deletion identified in an Italian HPT-JT family. Age at onset < 41.5 ys and Ca2+ > 13.96 mg/dL are predictive for the presence of a CDC73 genetic lesion.

Should all patients with hyperparathyroidism be screened for a CDC73 mutation?

SummaryPrimary hyperparathyroidism (PH) is a common endocrine abnormality and may occur as part of a genetic syndrome. Inactivating mutations of the tumour suppressor gene CDC73 have been identified as accounting for a large percentage of hyperparathyroidism-jaw tumour syndrome (HPT-JT) cases and to a lesser degree account for familial isolated hyperparathyroidism (FIHP) cases. Reports of CDC73 whole gene deletions are exceedingly rare. We report the case of a 39 year-old woman with PH secondary to a parathyroid adenoma associated with a large chromosomal deletion (2.5 Mb) encompassing the entire CDC73 gene detected years after parathyroidectomy. This case highlights the necessity to screen young patients with hyperparathyroidism for an underlying genetic aetiology. It also demonstrates that molecular testing for this disorder should contain techniques that can detect large deletions.Learning points:Necessity of genetic screening for young people with hyperparathyroidism.Importance of screening for large, including whole gene CDC73 deletions.Surveillance for patients with CDC73 gene mutations includes regular calcium and parathyroid hormone levels, dental assessments and imaging for uterine and renal tumours.

Parathyroid carcinoma: a clinical and genetic perspective.

Parathyroid carcinoma (PC) is a rare neoplasia difficult to diagnose preoperatively. It mainly occurs as a sporadic disease but also as part of familial PHPT. At variance with patients with the benign counterpart, the phenotype of these patients is characterized by a severe primary hyperparathyroidism (PHPT). The clinical features are mostly due to the effects of the excessive secretion of PTH by the functioning tumor and hypercalcemia rather than to the tumor burden. The prognosis is poor and unmanageable hypercalcemia accounts for death in the majority of cases. The best chance of cure is surgery, although persistent or recurrent disease occurs in about 50% of patients. Somatic loss-of-function mutations of CDC73 gene, encoding parafibromin, are the most frequent genetic alterations occurring in PCs. Mutations of the PRUNE2 gene, alterations of the PI3K/AKT/mTOR pathway and amplification of the CCND1 gene have been recently detected in PCs. Alteration of microRNA profile and methylation pattern have been identified in PCs. The recent studies have better defined the genomic landscape of PCs and represent major progress toward a full molecular characterization of this neoplasia and development of novel therapeutic options.

CDC73 gene mutations in sporadic ossifying fibroma of the jaws.

BackgroundThe tumor suppressor gene CDC73 was found to be associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT), which is characterized by parathyroid adenoma or carcinoma, ossifying fibroma (OF) of the jaws, and renal and uterine lesions. Mutations in CDC73 have also been frequently detected in sporadic parathyroid carcinomas and renal tumors. However, the prevalence and range of CDC73 mutations in sporadic OFs have not been established.MethodsWe directly sequenced coding and flanking splice junctional regions of CDC73 in 40 cases of sporadic OF of the jaws. We also used immunohistochemistry to detect parafibromin, the protein product of CDC73, in those cases.ResultsTwo novel CDC73 mutations were identified in 2 of the 40 cases (5 %). Both were somatic mutations located in exon 1 of the coding region. Strong parafibromin expression was detected in all 40 cases, irrespective of the presence of CDC73 mutations.ConclusionsMutations inCDC73 were rare in sporadic OF of the jaws, but may affect the pathogenesis of a small subset of tumors of this type.

Molecular and genetic features of primary hyperparathyroidism in young patients

When primary hyperparathyroidism (PHPT) is diagnosed in a young patient in the absence of other clinical manifestations differential diagnosis between a sporadic form of PHPT and PHPT as the first manifestation of one of hereditary syndromes may be challenging. Diagnosis of sporadic or hereditary PHPT determines the extent of surgical intervention, a strategy for further observation and treatment, and the need for examination and treatment of first-degree relatives. Aim of the study — to determine genetic characteristics of PHPT with manifestation at a young age (&lt;40 years old) with clinically sporadic PHPT and familial isolated hyperparathyroidism (FIHP).Material and methods. 40 patients with manifestation of PHPT at the age younger than 40 years, 4 of which with FIHP, were included in the study. In 11 patients Sanger sequencing of MEN1 gene was performed (ABI 3130 Genetic Analyser, «Applied Biosystems», USA). 37 patients underwent next-generation sequencing (NGS) (Ion Torrent PGM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). Results. In 3 (7,5%) patients (1 of which with FIHP) we revealed germline heterozygous mutations in MEN1 gene: in exon 9 p.D418N, exon 3 p.R176Q, intron 3 с.654+1G&gt;A. In 4 (4/40, 10%) patients we revealed germline heterozygous mutations in CDC73 gene: 3 nonsense mutations in patients with parathyroid carcinoma — in exon 3 p.R91X, exon 6 p.Q166X, exon 7 p.R229X, and 1 missense mutation in a patient with parathyroid hyperplasia in exon 8 p.R263C. Conclusions. In the majority of cases (75%) PHPT in young patients without positive family history is sporadic. Search for germline mutations in the genes, leading to development of hereditary forms of PHPT (first of all in MEN1 and CDC73), is appropriate in young patients with positive family history, or when positive family history may be suspected, and in patients with parathyroid carcinoma. In the majority (75%) of FIHP cases search for other, probably yet unknown, genes is necessary.

HRPT2- (CDC73) Related Hereditary Hyperparathyroidism: A Case Series From Western India

To describe a case series of HRPT2- (CDC73) related hereditary primary hyperparathyroidism (PHPT) from western India. We present a case series of 4 families (7 patients) with PHPT caused by CDC73 gene mutations. The mean age of presentation of the 4 index cases was 27.25 ± 9.8 years. Two family members were identified through biochemical screening (Cases 1b and 2b), while 1 mutation-positive family member did not manifest any features of PHPT or hyperparathyroidism jaw tumor syndrome (HPT-JT) syndrome (Case 2c). Biochemistry showed increased serum calcium (mean: 13.21 ± 1.24 mg/dL), low serum phosphorus (mean: 1.78 ± 0.44 mg/dL), and high parathyroid hormone (PTH, mean: 936 ± 586.9 pg/mL). All patients had a uniglandular presentation and underwent single adenoma excision initially except Cases 2a and 2b, who underwent subtotal parathyroidectomy at baseline. Two cases experienced PHPT recurrence (Cases 3 and 4), while 1 remained uncured due to parathyroid carcinoma (Case 1a). Other associated syndromic features like ossifying jaw fibromas were present in 2 patients, renal cysts in 3 patients, and uterine involvement in 2 patients. Two families had novel germline CDC73 mutations (Families 1 and 3), while the other 2 had reported mutations. Family 2 had familial isolated PHPT without any other features of HPT-JT syndrome. Our findings reaffirm the need for genetic analysis of patients with PHPT, especially those with younger age of disease onset; recurrent disease; and associated features like polycystic kidneys, endometrial involvement, ossifying jaw tumors, or parathyroid carcinoma.

Novel nonsense CDC73 mutations in Chinese patients with parathyroid tumors

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease characterized by the occurrences of parathyroid tumors and ossifying fibroma of maxilla/mandible. It is caused by mutations in CDC73 gene and mutation carriers are at increased risk of parathyroid carcinoma. Hyperparathyroidism could be the sole manifestation. We reported two Chinese patients having parathyroid neoplasm with equivocal malignant potential and parathyroid carcinoma respectively with both germline and somatic CDC73 mutations detected. Both of them presented with severe hypercalcemia and primary hyperparathyroidism with no other HPT-JT associated tumors and negative family history. We identified one novel germline mutation CDC73 NM_024529.4: c.1475G>A; NP_078805.3: p.Trp492X and one novel somatic mutation CDC73 NM_024529.4: c.142G>T; NP_078805.3: p.Glu48X. The other germline mutation CDC73 NM_024529.4: c.226C>T; NP_078805.3: p.Arg76X and somatic mutation CDC73 NM_024529.4: c.85delG; NP_078805.3: p.Glu29SerfsX8 were previously reported. This is the first report of CDC73 mutations in the Chinese population. Genetic analysis is reliable to confirm the underlying hereditary basis of hyperparathyroidism. By identification of mutations, the patient and the family members could benefit from regular surveillance for early detection of tumors.