The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred

Abstract

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disease characterized by the occurrence of parathyroid tumours and fibro-osseous tumours of the jaw bones. Some HPT-JT patients may also develop renal abnormalities, which include Wilms' tumours, hamartomas and polycystic disease. The HPT-JT gene has been mapped to chromosome 1q25-q31, and we report the clinical and genetic findings in a kindred from central Portugal. HPT-JT was observed in six members from three generations; all had primary hyperparathyroidism (five had parathyroid adenomas, one a parathyroid carcinoma). Ossifying jaw fibromas affecting the maxilla and/or mandible were observed in 5/6. Renal cysts (<2.5 cm) were observed in four. Genetic studies using 18 polymorphic loci from chromosome 1q25-q31, together with leukocyte DNA from 11 family members and tumour DNA from three parathyroids (two adenomas and one carcinoma), revealed loss of tumour heterozygosity in the parathyroid carcinoma only, and the retained haplotype was found to cosegregate with the disease in the six affected members. A new Portuguese kindred with the HPT-JT syndrome that maps to chromosome 1q25-q31 has been identified, and these findings will help in the further characterization of this inherited disorder.

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

“…To date, less than 40 families with HPT-JT have been reported in the literature (Carpten et al, 2002;Cavaco et al, 2004). The most common renal manifestation of this syndrome are cystic lesions, ranging from a few minor cysts to bilateral polycysts (Haven et al, 2000;Cavaco et al, 2001). Different renal tumors have been described to be associated with this syndrome, including mixed epithelial-stromal tumors (Teh et al, 1996), adult Wilms tumors (Kakinuma et al, 1994;Szabo et al, 1995), papillary RCC and multiple renal cell adenomas (Haven et al, 2000).…”

Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors

“…The hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by the occurrence of parathyroid tumors in association with ossifying fibromas of the maxilla and/or mandible (MIM] 145001) [Cavaco et al, 2001;Jackson et al, 1990;Szabo et al, 1995;Teh et al, 1996]. In addition, patients may develop other manifestations, most commonly renal and uterine tumors [Bradley et al, 2005b;Carpten et al, 2002;Cavaco et al, 2001;Haven et al, 2000;Hobbs et al, 1999;Szabo et al, 1995;Teh et al, 1996Teh et al, , 1998].…”

“…In addition, patients may develop other manifestations, most commonly renal and uterine tumors [Bradley et al, 2005b;Carpten et al, 2002;Cavaco et al, 2001;Haven et al, 2000;Hobbs et al, 1999;Szabo et al, 1995;Teh et al, 1996Teh et al, , 1998]. Parathyroid tumors, detectable by hypercalcaemia, occur in $95% of patients and are typically the first manifestation of disease Marx, 2000].…”

Parafibromin is a nuclear protein with a functional monopartite nuclear localization signal

“…Mutations of the gene encoding parafibromin, a 531 amino-acid protein, are associated with hereditary and non-hereditary forms of parathyroid carcinomas, and the hyperparathyroidism-jaw tumour (HPT-JT) syndrome, which is characterized by the combined occurrence of parathyroid tumours and ossifying fibromas of the jaw (Cavaco et al, 2001;Carpten et al, 2002;Howell et al, 2003;Shattuck et al, 2003). In addition, some patients with the HPT-JT syndrome may also develop uterine tumours and renal abnormalities, which include Wilms' tumours, hamartomas and polycystic disease (Szabo et al, 1995;Teh et al, 1996;Haven et al, 2000;Cavaco et al, 2001;Bradley et al, 2005).…”

“…In addition, some patients with the HPT-JT syndrome may also develop uterine tumours and renal abnormalities, which include Wilms' tumours, hamartomas and polycystic disease (Szabo et al, 1995;Teh et al, 1996;Haven et al, 2000;Cavaco et al, 2001;Bradley et al, 2005). Other tumours, including Hurthle cell thyroid adenomas, pancreatic adenocarcinomas and testicular mixed germ cell tumours have also been reported in some patients with HPT-JT (Haven et al, 2000;Bradley et al, 2005).…”