Increased gene dosage at Xq26-q27 is associated with X-linked hypopituitarism.

We have identified a novel interstitial duplication at Xq26.1-q27.3 in a previously reported family with X-linked recessive hypopituitarism [1]. Mapping of the duplication was carried out using interphase FISH analysis of over 60 bacterial genomic clones from Xq25-q28. The proximal and distal breakpoints of the duplication are contained within the 432N13 and 91O18 clones, respectively, and are separated by approximately 9 Mb. Comparison with a recently published 13-Mb duplication in another XH family [2] indicated that the duplication break-points in these families were different. Therefore, we conclude that X-linked hypopituitarism is caused by increased dosage of a gene that is critical for pituitary development and that the causative gene is located within the 9-Mb duplicated region that we have defined.