Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. 1083 33

Combined pituitary hormone deficiency (CPHD) can be caused by mutation of the pituitary transcription factors POU1F1 or PROP1. More recently mutations in the HESX1, the LHX3 and LHX4 transcription factor genes have also been described as a cause in patients with CPHD. In most patients the disorder is characterized by an impaired production of GH, TSH, PRL and gonadotropins. In some cases of CPHD adrenocorticotropin deficiency is also present. We report the progressive CPHD and its molecular etiology in a woman with CPHD presenting with first symptoms of ACTH/cortisol deficiency at the age of 48 years. The 49 year old patient's initial symptoms were growth retardation at the age of 2 years and symptoms of hypothyroidism at the age of 5 years. The patient never entered puberty spontaneously. No familial history of delayed puberty, growth retardation or other symptoms of CPHD were present. At the age of 48 years the patient presented with the first symptoms of hypocortisolism such as recurring hypoglycaemias and hyponatriaemia with coma. Cortisol, ACTH, TSH, fT3, fT4 and GH as well as LH, FSH and PRL were measured in basal conditions. GH, cortisol and ACTH were also measured in response to an Insulin Tolerance Test. Molecular analysis was performed by PCR amplification and sequencing of exon 1-3 of the PROP1 gene. The patient had insufficiencies of TSH, LH, FSH and GH. PRL was normal. Serum cortisol was low and basal ACTH was normal. However, there were no responses of cortisol, ACTH and GH to hypoglycaemia. Magnetic resonance imaging showed a hypoplastic anterior pituitary lobe. Direct sequencing revealed a homozygous 2 base-pair deletion 301-302delAG in exon 2 of the PROP1 gene. This case suggests that in patients with CPHD ACTH producing cells may be involved at a rather late age.
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PMID:Adrenocorticotrope deficiency with clinical evidence for late onset in combined pituitary hormone deficiency caused by a homozygous 301-302delAG mutation of the PROP1 gene. 1281 7