Limits...
Molecular and Clinical Findings in Patients with LHX4 and OTX2 Mutations.

Tajima T, Ishizu K, Nakamura A - Clin Pediatr Endocrinol (2013)

Bottom Line: These findings indicate that the other genetic and/or environmental factors influence the phenotype.Furthermore, the causes in many patients with CPHD have not yet been determined.Therefore, continuing efforts for the clarification of the etiology are necessary.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Hokkaido, Japan.

ABSTRACT
The pituitary gland produces hormones that play important roles in both the development and homeostasis of the body. Ontogeny of the anterior and posterior pituitary is orchestrated by inputs from neighboring tissues, cellular signaling molecules and transcription factors. Disruption of expression or function of these factors has been implicated in the etiology of combined pituitary hormone deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, OTX2, SOX2, SOX3 and GLI2. This review focuses on summarizing most recent mutations in LHX4 and OTX2 responsible for pituitary hormone deficiency. In both genetic defects of LHX4 and OTX2, there is high variability in clinical manifestations even in the same family. In addition, there is no clear phenotype-genotype correlation. These findings indicate that the other genetic and/or environmental factors influence the phenotype. In addition, the variability might reflect a plasticity during pituitary development and maintenance. Over the past two decades, a genetic basis for pituitary hormone deficiency and the mechanism of pituitary development have been clarified. It should be kept in mind that this review is not comprehensive, and defects of other transcriptional factors have been described in patients with CPHD. Furthermore, the causes in many patients with CPHD have not yet been determined. Therefore, continuing efforts for the clarification of the etiology are necessary.

No MeSH data available.


Related in: MedlinePlus

Schema of LHX4 genomic organization and protein structure. Thelocation of reported mutations is shown. Mutations of introns are indicated by thearrows. Missense mutations and a frameshift mutation are indicated by black dots.Numbers next to the protein indicate amino acid positions of domain boundaries. Whiteboxes, exon; LIM, LIM domains; HD homeodomain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3756183&req=5

fig_001: Schema of LHX4 genomic organization and protein structure. Thelocation of reported mutations is shown. Mutations of introns are indicated by thearrows. Missense mutations and a frameshift mutation are indicated by black dots.Numbers next to the protein indicate amino acid positions of domain boundaries. Whiteboxes, exon; LIM, LIM domains; HD homeodomain.

Mentions: Mutations of LHX4 and clinical characteristics are summarized in Fig. 1Fig. 1


Molecular and Clinical Findings in Patients with LHX4 and OTX2 Mutations.

Tajima T, Ishizu K, Nakamura A - Clin Pediatr Endocrinol (2013)

Schema of LHX4 genomic organization and protein structure. Thelocation of reported mutations is shown. Mutations of introns are indicated by thearrows. Missense mutations and a frameshift mutation are indicated by black dots.Numbers next to the protein indicate amino acid positions of domain boundaries. Whiteboxes, exon; LIM, LIM domains; HD homeodomain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756183&req=5

fig_001: Schema of LHX4 genomic organization and protein structure. Thelocation of reported mutations is shown. Mutations of introns are indicated by thearrows. Missense mutations and a frameshift mutation are indicated by black dots.Numbers next to the protein indicate amino acid positions of domain boundaries. Whiteboxes, exon; LIM, LIM domains; HD homeodomain.
Mentions: Mutations of LHX4 and clinical characteristics are summarized in Fig. 1Fig. 1

Bottom Line: These findings indicate that the other genetic and/or environmental factors influence the phenotype.Furthermore, the causes in many patients with CPHD have not yet been determined.Therefore, continuing efforts for the clarification of the etiology are necessary.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Hokkaido, Japan.

ABSTRACT
The pituitary gland produces hormones that play important roles in both the development and homeostasis of the body. Ontogeny of the anterior and posterior pituitary is orchestrated by inputs from neighboring tissues, cellular signaling molecules and transcription factors. Disruption of expression or function of these factors has been implicated in the etiology of combined pituitary hormone deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, OTX2, SOX2, SOX3 and GLI2. This review focuses on summarizing most recent mutations in LHX4 and OTX2 responsible for pituitary hormone deficiency. In both genetic defects of LHX4 and OTX2, there is high variability in clinical manifestations even in the same family. In addition, there is no clear phenotype-genotype correlation. These findings indicate that the other genetic and/or environmental factors influence the phenotype. In addition, the variability might reflect a plasticity during pituitary development and maintenance. Over the past two decades, a genetic basis for pituitary hormone deficiency and the mechanism of pituitary development have been clarified. It should be kept in mind that this review is not comprehensive, and defects of other transcriptional factors have been described in patients with CPHD. Furthermore, the causes in many patients with CPHD have not yet been determined. Therefore, continuing efforts for the clarification of the etiology are necessary.

No MeSH data available.


Related in: MedlinePlus