| First Author | Netchine I | Year | 2000 |
| Journal | Nat Genet | Volume | 25 |
| Issue | 2 | Pages | 182-6 |
| PubMed ID | 10835633 | Mgi Jnum | J:62550 |
| Mgi Id | MGI:1859079 | Doi | 10.1038/76041 |
| Citation | Netchine I, et al. (2000) Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. Nat Genet 25(2):182-6 |
| abstractText | Combined pituitary hormone deficiency (CPHD) has been linked with rare abnormalities in genes encoding transcription factors necessary for pituitary development. We have isolated LHX3, a gene involved in a new syndrome, using a candidate-gene approach developed on the basis of documented pituitary abnormalities of a recessive lethal mutation in mice generated by targeted disruption of Lhx3 (ref. 2). LHX3, encoding a member of the LIM class of homeodomain proteins, consists of at least six exons located at 9q34. We identified a homozygous LHX3 defect in patients of two unrelated consanguineous families displaying a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation. Two of these patients also displayed a severe pituitary hypoplasia, whereas one patient presented secondarily with an enlarged anterior pituitary. These LHX3 mutations consist of a missense mutation (Y116C) in the LIM2 domain at a phylogenetically conserved residue and an intragenic deletion predicting a severely truncated protein lacking the entire homeodomain. These data are consistent with function of LHX3 in the proper development of all anterior pituitary cell types, except corticotropes, and extrapituitary structures. |
