Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation inCDKN1B

Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes:MEN1, CASR, orCDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations inCDKN1Band those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novelCDKN1Bgermline mutation (heterozygote for a missense mutation in exon 1 of theCDKN1Bgene (c.378G>C) (p.E126D)). The implication from this case is thatCDKN1Bgermline mutations may be associated with PHPT at an earlier age than previously thought.

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Infantile Onset Hypertrophic Cardiomyopathy Secondary to PRKAG2 Gene Mutation is Associated with Poor Prognosis

Journal of Pediatric Genetics ◽

10.1055/s-0038-1657763 ◽

2018 ◽

Vol 07 (04) ◽

pp. 180-184

Author(s):

Kishore Raja ◽

Ashish Garg ◽

Deborah Barbouth ◽

Paolo Rusconi ◽

Sudheer Gorla

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Missense Mutation ◽

Gene Mutation ◽

Early Onset ◽

Poor Prognosis ◽

Metabolic Disorders ◽

Age Of Onset ◽

Case Reports ◽

Genetic Syndromes ◽

Prevalent Form

AbstractHypertrophic cardiomyopathy (HCM) is the second most prevalent form of cardiomyopathy in children. The etiology of the HCM is heterogeneous, so is the age of onset of symptoms. The HCM associated with metabolic disorders and genetic syndromes presents early in childhood. There are very few case reports of early-onset infantile HCM secondary to the PRKAG2 gene. Here, we report a case of HCM in a neonate diagnosed prenatally and eventually diagnosed with a missense mutation in the PRKAG2 gene.

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Abstract #805292: Early Onset Primary Hyperparathyroidism with CD73 Gene Mutation

Endocrine Practice ◽

10.1016/s1530-891x(20)39617-8 ◽

2020 ◽

Vol 26 ◽

pp. 59-60

Author(s):

Ana Del Carmen Rivadeneira

Keyword(s):

Primary Hyperparathyroidism ◽

Gene Mutation ◽

Early Onset

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Clinical Characteristics of and Relationship Between Metabolic Components and Renal Function Among Patients with Early-onset Juvenile Tophaceous Gout

The Journal of Rheumatology ◽

10.3899/jrheum.131240 ◽

2014 ◽

Vol 41 (9) ◽

pp. 1878-1883 ◽

Cited By ~ 13

Author(s):

Chuan-Chin Lu ◽

Shyi-Kuen Wu ◽

Han-Yu Chen ◽

Wei-Sheng Chung ◽

Meng-Chih Lee ◽

...

Keyword(s):

Renal Function ◽

Early Onset ◽

Clinical Characteristics ◽

Middle Age ◽

Age Of Onset ◽

Relevant Information ◽

Serum Urate ◽

Common Site ◽

Tophaceous Gout ◽

Impaired Liver

Objective.Age of onset of gout has recently decreased; however, patients with early-onset gout remain uncommon, and relevant information is scant. We hypothesized that these patients might exhibit differences in serum urates and other comorbidities compared with adult-onset patients.Methods.Early-onset gout patients (i.e., juveniles) with (n = 40) and without tophi (n = 47) were enrolled for study. Their clinical characteristics were compared with those of 353 patients with middle-age-onset tophaceous gout and 64 age-matched healthy participants.Results.Early-onset gout patients with tophi exhibited significantly higher body mass indices and serum urate levels and lower estimated glomerular filtration rates (eGFR) than did those without tophi. Early-onset gout patients with or without tophi demonstrated significantly abnormal lipid profiles and impaired liver or renal function compared with healthy patients. Serum urate levels and gout duration were identified as the principal determinants of tophi development. The presence of tophi might be crucial in decreasing eGFR, which is inversely related to tophi duration or gout duration. Unexpectedly, the most common site of initial gout attacks in early-onset tophaceous gout patients was the ankle, not the toe, which was the most common site in middle-age-onset tophaceous gout patients. The most common site of first tophi occurrence in early-onset patients was a finger, not a toe, which was the most common site in middle-age-onset patients.Conclusion.Early-onset tophaceous gout patients are more likely to exhibit comorbidities and renal dysfunction than middle-age-onset patients and exhibit distinct first sites of gout attack and tophi occurrence patterns.

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Somatic and germline mutation profiles of Chinese breast cancer patients younger than 35.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.554 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 554-554

Author(s):

Ning Liao ◽

Guo-Chun Zhang ◽

Xiaoqing Chen ◽

Weikai Xiao ◽

Jianguo Lai ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Patients ◽

Germline Mutation ◽

Early Onset ◽

Chinese Women ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Younger Women

554 Background: Limited studies have investigated the molecular underpinnings driving breast cancer development in Chinese younger women. Based from our previous data, more Chinese women are diagnosed with early-onset breast cancer than in the West. In our study, we aim to investigate the comprehensive mutational profile of Chinese women 35 years old and younger (≤35y) diagnosed with breast cancer. Methods: Targeted sequencing was performed on surgically-removed tumor tissues and blood samples collected from 589 women diagnosed with stage I-III breast cancer of various molecular subtypes at the Guangdong Provincial People’s Hospital (GPDH) using a gene panel interrogating 520 cancer-related genes. We compared the data of 53 women aged ≤35y from our cohort to the data from 33 breast cancer patients aged ≤35y included in The Cancer Genome Atlas (TCGA) dataset. Results: Among the women aged ≤35y with early-stage breast cancer from both cohorts, our cohort had more number of hormone receptor-positive (HR+) patients (GPDH, 72% vs. TCGA, 61%, P< 0.001). Analysis revealed an overall mutation detection rate of 98% in our cohort, with mutations affecting genes involved in the PI3K pathway (47%) and cell cycle pathway (23%). TP53 and PIK3CA were the most commonly mutated genes, with mutation rates of 51% and 25% from our cohort. No statistical difference in mutation profile was found between GPDH and TCGA cohorts. Moreover, germline mutations considered as pathogenic and likely pathogenic (P/LP) in breast cancer susceptibility genes including BRCA1 (n = 4), BRCA2 (n = 2), PALB2 (n = 1), PMS2 (n = 1), PTEN (n = 1), and ATM (n = 1) were detected from 18.9% (10/53) of the patients from our cohort. Women aged ≤35y had significantly more germline BRCA1 mutations than patients > 35y from our cohort (7.5%, 4/53 vs. 2.1%, 11/536 P= 0.049). Conclusions: Our study has identified the involvement of PI3K and cell cycle as the two key pathways in the early development of breast tumors in younger women. In addition, our results also support the role of P/LP germline mutations in breast oncogenesis in Chinese patients with early-onset breast cancer, indicating the need to include a more comprehensive germline mutation screening in our population.

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Mutation screening of germline TP53 mutations in high-risk Chinese breast cancer patients

BMC Cancer ◽

10.1186/s12885-020-07476-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Ava Kwong ◽

Vivian Yvonne Shin ◽

Cecilia Y. S. Ho ◽

Chun Hang Au ◽

Thomas P. Slavin ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Cancer Patients ◽

Germline Mutation ◽

Early Onset ◽

Mutation Screening ◽

Germline Mutations ◽

Breast Cancer Patients ◽

History Of ◽

History Of Cancer

Abstract Background Germline TP53 mutations are associated with Li-Fraumeni syndrome, a severe and rare hereditary cancer syndrome. Despite the rarity of germline TP53 mutations, the clinical implication for mutation carriers and their families is significant. The risk management of TP53 germline mutation carriers is more stringent than BRCA carriers, and radiotherapy should be avoided when possible. Methods TP53 gene mutation screening was performed in 2538 Chinese breast cancer patients who tested negative for BRCA mutations. Results Twenty TP53 mutations were identified with high next-generation sequencing concerning for germline mutations in Chinese breast cancer families. The majorities of the TP53 carriers had early-onset, hormone receptor-positive breast cancer, and had strong family history of cancer. Among all, 11 patients carried a germline mutation and 6 of which were likely de novo germline mutations. In addition, 1 case was suspected to be induced by chemotherapy or radiation, as this patient had no significant family history of cancer and aberrant clonal expansion can commonly include TP53 mutations. Furthermore, we have identified one mosaic LFS case. Two novel mutations (c.524_547dup and c.529_546del) were identified in patients with early-onset. Conclusions In view of the high lifetime risk of malignancy, identification of patients with germline TP53 mutations are important for clinicians to aid in accurate risk assessment and offer surveillance for patients and their families.

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