A Kindred of Familial Acromegaly without Evidence for Linkage to MEN-1 Locus

抄録

Familial acromegaly (FA) is a rare inherited disease characterized by clustering of somatotrophic adenomas and acromegaly within a family without other manifestations of multiple endocrine neoplasia-type 1 (MEN-1). The genetic basis of this pituitary-specific phenotype is largely unknown, and its relationship to the MEN-1 locus on chromosome 11q13 also remains unclear. To test the hypothesis that FA results from a germline mutation of the MEN-1 locus, we performed a linkage analysis in a Japanese family with 2 members showing manifestations of acromegaly due to somatotroph adenomas. We also examined the adenoma of one patient for loss of heterozygosity (LOH) at 11q13 locus and for the presence of mutations of codon 201 and 227 in the gene for Gsα. Our results provided no evidence that either germline alterations of the MEN-1 locus, LOH at 11q13, or somatic mutation of Gsα plays a causative role in the development of somatotroph adenomas in our FA family. Together with the previous reports, these results suggest that there are at least two distinct subgroups of FA: one that results from a mutation in MEN-1 locus and the other whose causative gene is located outside the 11q13 locus.