Supplementary Material for: A Familial Case of a Whole Germline <b><i>CDC73</i></b> Deletion Discordant for Primary Hyperparathyroidism

<b><i>Introduction:</i></b> Primary hyperparathyroidism (PHPT) occurs as part of familial syndromes, including <i>CDC73</i>-related disorders caused by germline pathogenic variants of<i></i> the<i> CDC73</i> gene, particularly in early adulthood. Herein, we report a familial case of a whole germline <i>CDC73</i> deletion discordant for PHPT. <b><i>Case Description:</i></b> 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 <i>CDC73</i>. 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 <i>CDC73</i> 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. <b><i>Conclusions:</i></b> These data clearly demonstrate the Knudson two-hit theory from a molecular viewpoint. Phenotypic variability and incomplete penetrance of <i>CDC73</i>-related disorders, even if caused by a gross deletion, should be noted in a clinical setting.