Screening of LHX2 in patients presenting growth retardation with posterior pituitary and ocular abnormalities

Abstract

Background: In humans, pituitary hormone deficiency may be part of a syndrome including extrapituitary defects like ocular abnormalities. Very few genes have been linked to this particular phenotype. In the mouse, Lhx2, which encodes a member of the LIM (Lin-11, Isl-1, and Mec-3) class of homeodomain proteins, was shown to be expressed during early development in the posterior pituitary, eye, and liver, and its expression persists in adulthood in the central nervous system Lhx2 K/K mice display absence of posterior pituitary and intermediate lobes, malformation of the anterior lobe, anophthalmia, and they die from anemia. Methods: We tested the implication of the LHX2 gene in patients presenting pituitary hormone deficiency associated with ectopic or nonvisible posterior pituitary and developmental ocular defects. A cohort of 59 patients, including two familial cases, was studied. Direct sequencing of the LHX2 coding sequence and intron/exon boundaries was performed. LHX2 transcriptional activity on several pituitary promoters (AGSU, PRL, POU1F1, and TSHB) was tested in vitro. Results: Six heterozygous sequence variations were identified, among which two are novel missense changes (p.Ala203Thr and p.Val333Met). In vitro, LHX2 activates transcription of TSHB, PRL, and POU1F1 promoters in the HEK293 cell line. A synergistic action of POU1F1 and LHX2 was also shown on these promoters. The two missense variations were tested and no significant difference was observed, leading to the conclusion that they are not deleterious. Conclusions: These results suggest that if LHX2 is involved in pituitary hormone deficiency associated with posterior pituitary and ocular defects, it would be a rare cause of this disease condition.

Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features

“…Recent analyses of human embryonic stem cells demonstrated that it also has a crucial role in human brain morphogenesis [ 27 , 28 ]. There is evidence that LHX2 is expressed in the early neural lineage, which affects signaling pathways fundamental for early lineage differentiation in the human brain via regulation of the neural transcription factors from the SIX gene family [ 28 , 29 ]. Our results constitute confirmation of this observation.…”

Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism

“…Genes involved in pituitary development such as HESX1 , LHX3 , LHX4 , PROP1 , POU1F1 , SOX3 OTX2 and those expressed along the somatotropic axis such as GH1 , GHRHR and GHSR constitute two groups of genes in which mutations were identified . Some other genes encoding proteins obviously involved in GH secretion like GHRH or in pituitary development like LHX2 have been screened in several cohorts, but no mutation has been found.…”

Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer

“…Lhx2 is up-regulated in several cancer transcriptome databases in mouse models of breast cancer (Chou and Yang, 2006) and neuroendocrine carcinoma (Zhao et al. , 2010; Perez et al. , 2012).…”