The hyperparathyroidism-jaw tumour (HPT-JT) syndrome
2006
The hyperparathyroidsim-jaw tumour (HPT-JT) syndrome is an
autosomal dominant disorder characterised by the occurence
of parathyroid tumours, which may be carcinomas in approximately
15% of patients, and ossifying fibromas, that usually affect
the maxilla and/or mandible. More than 15% of HPT-JT patients
may also develop renal and uterine abnormalities. The
gene causing HPT-JT, referred to as HRPT2, is located on
chromosome 1q31.2 and consists of 17 exons that encode a
531 amino-acid protein, designated PARAFIBROMIN. PARAFIBROMIN
has been shown to be associated with the human homologue
of the yeast Paf1 protein complex which interacts
with RNA polymerase II, and as part of this protein complex,
PARAFIBROMIN may regulate post-transcriptional events and
histone modification. To date 63 HRPT2 mutations have been
reported and over 80% of these are nonsense or frameshift
mutations that are predicted to result in a functional loss of the
PARAFIBROMIN protein because of premature truncation.
Moreover, loss of heterozygosity involving chromosome 1q
and somatic HRPT2 mutations have been observed in some
HPT-JT associated tumours and this is consistent with a tumour
suppressor role for HRPT2. HRPT2 somatic mutations also
frequently occur in parathyroid carcinomas but not adenomas.
In addition, patients with ‘non-familial’ parathyroid carcinomas
may harbour germline HRPT2 mutations. The HRPT2
mutations are scattered throughout the coding region, and
there is an absence of a genotype-phenotype correlation. The
results of these studies have enabled guidelines for the clinical
management and genetic screening for HPT-JT kindreds and
patients with parathyroid carcinoma to be proposed
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