OBJECTIVES: Investigation of small numbers of parathyroid tumours by X-chromosome inactivation analysis suggests that the majority of them are monoclonal lesions most likely caused by a somatic mutation. Somatic mutations in the MEN1 gene located on chromosome 11q13 have recently been identified in 12-17% of solitary parathyroid tumours in patients with sporadic primary hyperparathyroidism, and they may be the precipitating genetic defect leading to monoclonal cell proliferation in these tumours. DESIGN: To determine the prevalence of MEN1 gene mutations in monoclonal parathyroid neoplasias we investigated 33 parathyroid tumours of patients with primary hyperparathyroidism for clonality and mutations in the MEN1 gene. METHODS: X-chromosome inactivation analysis was used to assess the clonal status of the tumours, direct sequencing of the complete coding region was applied to identify mutations in the MEN1 gene. RESULTS: Twenty-eight female patients (26 patients with solitary adenoma, 2 patients with hyperplasia) were informative for the polymorphism of the androgen receptor on the X-chromosome and could be tested for inactivation pattern. Nineteen of twenty-six (73%) solitary adenomas were monoclonal. Somatic mutations in the MEN1 gene were identified in nine cases. Six of them were found in the relatively large second exon of the MEN1 gene (A49D, 193del36, 402delC, 482del22, 547delT, W126X). One was found in exon 5 (904del9), one in exon 7 (Y327X) and one in exon 9 (R415X). Of the monoclonal tumours, 5 out of 19 (26%) harboured a somatic MEN1 gene mutation. CONCLUSIONS: In summary, 73% of the solitary parathyroid adenomas were monoclonal. In 26% of the monoclonal tumours a somatic MEN1 gene mutation has been identified. However, for 74% of monoclonal tumours of the parathyroids the underlying genetic defects are still not known.
MECP2 mutations in Danish patients with Rett syndrome: High frequency of mutations but no consistent correlations with clinical severity or with the X chromosome inactivation pattern