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

Naomi Hatabu, Naho Katori, Takeshi Sato, Naonori Maeda, Eri Suzuki, Osamu Komiyama, Hidemitsu Tsutsui, Toshitaka Nagao, Hana Nakauchi-Takahashi, Tatsuo Matsunaga, Tomohiro Ishii, Tomonobu Hasegawa, Kazuki Yamazawa

研究成果: Article査読

1 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)56-63
ページ数8
ジャーナルHormone Research in Paediatrics
92
1
DOI
出版ステータスPublished - 2019 12 1

ASJC Scopus subject areas

  • 小児科学、周産期医学および子どもの健康
  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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