A Familial Case of a Whole Germline CDC73 Deletion Discordant for Primary Hyperparathyroidism.

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A Familial Case of a Whole Germline CDC73 Deletion Discordant for Primary Hyperparathyroidism.

Horm Res Paediatr. 2019 Feb 08;:1-8

Authors: Hatabu N, Katori N, Sato T, Maeda N, Suzuki E, Komiyama O, Tsutsui H, Nagao T, Nakauchi-Takahashi H, Matsunaga T, Ishii T, Hasegawa T, Yamazawa K

Abstract
INTRODUCTION: Primary hyperparathyroidism (PHPT) occurs as part of familial syndromes, including CDC73-related disorders caused by germline pathogenic variants of the CDC73 gene, particularly in early adulthood. Herein, we report a familial case of a whole germline CDC73 deletion discordant for PHPT.
CASE DESCRIPTION: A 15-year-old boy was admitted to our hospital because of persistent nausea and vomiting. Laboratory tests showed hypercalcemia (13.6 mg/dL), hypophosphatemia (2.4 mg/dL), and elevated intact PTH level (149 pg/mL). Imaging studies showed an enlarged single parathyroid gland. Thus, the diagnosis of PHPT was made. Microarray analysis of peripheral blood DNA showed a 3.4-Mb heterozygous deletion of 1q31 encompassing 11 genes, including CDC73. Total thyroidectomy/parathyroidectomy was performed; histology was compatible with parathyroid adenoma without any evidence of malignancy. DNA sequencing of the removed adenoma confirmed a hemizygous nonsense variant in the CDC73 gene in a mosaic manner, which was potentially involved in parathyroid tumorigenesis as the "second hit." Importantly, the same deletion was identified in his 52-year-old father who had an unremarkable medical history.
CONCLUSIONS: These data clearly demonstrate the Knudson two-hit theory from a molecular viewpoint. Phenotypic variability and incomplete penetrance of CDC73-related disorders, even if caused by a gross deletion, should be noted in a clinical setting.

PMID: 30739106 [PubMed - as supplied by publisher]

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