Large deletion at the CDC73 gene locus and search for predictive markers of the presence of a CDC73 genetic lesion

• Published in: Oncotarget Vol. 9; no. 29; pp. 20721 - 20733
• Main Authors: Muscarella, Lucia Anna, Turchetti, Daniela, Fontana, Andrea, Baorda, Filomena, Palumbo, Orazio, la Torre, Annamaria, de Martino, Danilo, Franco, Renato, Losito, Nunzia Simona, Repaci, Andrea, Pagotto, Uberto, Cinque, Luigia, Copetti, Massimiliano, Chiofalo, Maria Grazia, Pezzullo, Luciano, Graziano, Paolo, Scillitani, Alfredo, Guarnieri, Vito
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 17.04.2018
• Subjects: Research Paper; HPT-JT; large genomic deletion; early onset; CDC73
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.25067

The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the gene: it has been suggested that early onset of the disease and high Ca levels may predict the presence of a mutation. We searched for large deletions at the locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a gene mutation, clinical/histological diagnosis, age at onset, Ca , PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a gene mutation. A novel genomic deletion of the first 10 exons of the gene was found in a 3-generation HPT-JT family, confirmed by SNP array analysis. A classification tree built on the published data, showed the highest probability of having a mutation in subjects with age at the onset < 41.5 years (44/47 subjects, 93.6%, had the mutation). Whereas the lowest probability was found in subjects with age at the onset ≥ 41.5 years and Ca levels <13.96 mg/dL (7/20 subjects, 35.0%, had the mutation, odds ratio = 27.1, < 0.001). We report a novel large genomic CDC73 gene deletion identified in an Italian HPT-JT family. Age at onset < 41.5 ys and Ca > 13.96 mg/dL are predictive for the presence of a CDC73 genetic lesion.