Hyperparathyroidism-Jaw Tumor Syndrome Associated With Large-Scale 1q31 Deletion

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant cause of familial hyperparathyroidism associated with benign, ossifying fibromas of the maxillofacial bones and increased risk of parathyroid carcinoma. The putative tumor suppressor gene CDC73 has been implicated in the syndrome, with a multitude of inactivating mutations identified; however, HPT-JT due to large-scale deletion of the chromosomal region containing the gene is exceedingly rare, and the clinical significance of this variant remains unclear. We report the case of a 32-year-old woman with a history of mandibular ossifying fibroma who presented with primary hyperparathyroidism and was found to harbor a large-scale, germline deletion on chromosome 1q31, including the CDC73 locus. HPT-JT is associated with loss of function of the putative tumor suppressor gene CDC73. Over 100 mutations and small insertions/deletions have been identified within the gene, the majority of which result in premature truncation of the parafibromin protein product. We report a case of HPT-JT associated with a large chromosomal deletion (4.1 Mb) encompassing the CDC73 gene locus. In the future, molecular testing in this autosomal dominant disorder should use techniques that allow for the detection of large-scale deletions in addition to the more commonly observed mutations and smaller-scale copy number alterations. Further investigation is needed to determine whether HPT-JT associated with a large-scale deletion carries increased risk of malignancy relative to the more common truncating mutations and what the implications are for genetic counseling.