1q31.2 Deletion

Deletions of the 1q31.2 segment results in a condition called Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT). HPT-JT is characterized by parathyroid tumors, ossifying fibromas of the jaw bones, kidney lesions, and uterine lesions¹. These features can be attributed to the deletion of the CDC73 gene, which is included in the 1q31.2 region. CDC73 encodes a protein that is important for transcription regulation during the cell cycle and, when working properly, CDC73 works to inhibit cell growth and proliferation ^2,3. Deletion of CDC73 causes these tumors and growths associated with HPT-JT to occur.

Parathyroid tumors are a key finding of HPT-JT. These growths often result in hyperparathyroidism, causing individuals to have abnormal calcium metabolism¹. While less common, there have been individuals with deletions of CDC73 that have presented with parathyroid cancer⁴. These individuals may have symptoms including fatigue, depression, weight loss, nausea, abdominal pain, vomiting, and constipation⁴.

In addition to parathyroid tumors, many individuals also present with ossifying fibromas of the maxilla or mandible. Less commonly renal lesions and anomalies such as bilateral cysts, renal hamartomas, or Wilms tumor may also be present¹. Additionally, uterine lesions are another common growth identified. 

Although there are only a few key features of HPT-JT, there have yet to be any mutation-specific phenotype associated with CDC73¹. Both children and adults may present with clinical features should they have a deletion of 1q31.2, but what symptoms are present may vary from individual to individual even within the same family. Some may present with symptoms earlier in life, and others later². It is recommended that asymptomatic individuals with a 1q31.2 deletion receive periodic biochemical surveillance for hyperparathyroidism as well as tumor surveillance of the jaw, kidney, and uterus³.

References

¹Cascón A, Huarte-Mendicoa CV, Javier Leandro-García L, et al. (2011). Detection of the first gross CDC73 germline deletion in an HPT-JT syndrome family. Genes Chromosomes Cancer. 50(11):922–929.
²Blackburn J, Mulvey I, Nadar R, et al. (2022). Heterozygous CDC73 mutation causing hyperparathyroidism in children and adolescents: a report of 2 cases. J Pediatr Endocrinol Metab. 35(12):1547–1551.
³Guarnieri V, Seaberg RM, Kelly C, et al. (2017). Large intragenic deletion of CDC73 (exons 4-10) in a three-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family. BMC Med Genet. 18(1):83.
⁴Davidson JT, Lam CG, McGee RB, et al. (2016). Parathyroid Cancer in the Pediatric Patient. J Pediatr Hematol Oncol. 38(1):32–37.