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.
Solomon
Nicola M
NM
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia, 3052.
Nouri
Sara
S
Warne
Garry L
GL
Lagerström-Fermér
Maria
M
Forrest
Susan M
SM
Thomas
Paul Q
PQ
D004303:Dosage Compensation, Genetic; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D008040:Genetic Linkage; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D020161:Physical Chromosome Mapping; D014960:X Chromosome / Q000235:genetics