Study of the multiple endocrine neoplasia type 1, growth hormone-releasinghormone receptor, Gs alpha, and Gi2 alpha genes in isolated familial acromegaly

Familial acromegaly may occur as an isolated pituitary disorder or as a fea ture of hereditary syndromes, such as multiple endocrine neoplasia type 1 ( MEN1) or the Carney complex. Herein, we characterized a newly identified ki ndred with isolated acromegaly and searched for germline mutation in genes that have been associated with endocrine tumors [i.e. MEN1, Gs alpha (GNAS1 ), and Gi2 alpha (GNAI2)], as well as the GHRH receptor (GHRH-R) gene. Geno mic DNA was used to amplify exons 2-10 of MEN1, followed by dideoxy fingerp rinting mutation analysis and direct sequencing. The GHRH-R gene was analyz ed via direct sequencing of PCR-amplified fragments representing the coding exons and intron-exon junctions. To exclude mutation at hot spot areas of GNAS1 and GNAI2, exons 8 and 9 of GNAS1 and exons 5 and 6 of GNAI2 were amp lified and screened for mutation via denaturing gradient gel electrophoresi s. No mutations were detected in any of the four genes. The present data ex tend prior reports of the absence of mutation in MEN1, GHRH-R, and GNAS1 an d describe the first family with isolated acromegaly in which germline muta tion in GNAI2 has been searched.