RGD Reference Report - A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. - Rat Genome Database

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A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.

Authors: Lifton, RP  Dluhy, RG  Powers, M  Rich, GM  Cook, S  Ulick, S  Lalouel, JM 
Citation: Lifton RP, etal., Nature. 1992 Jan 16;355(6357):262-5.
RGD ID: 4891155
Pubmed: PMID:1731223   (View Abstract at PubMed)
DOI: DOI:10.1038/355262a0   (Journal Full-text)

Glucocorticoid-remediable aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension with variable hyperaldosteronism and by high levels of the abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol, which are all under control of adrenocorticotropic hormone and suppressible by glucocorticoids. These abnormalities could result from ectopic expression of aldosterone synthase, which is normally expressed only in adrenal glomerulosa, in the adrenal fasciculata. Genes encoding aldosterone synthase and steroid 11 beta-hydroxylase (expressed in both adrenal fasciculata and glomerulosa), which are 95% identical and lie on chromosome 8q (refs 7, 10), are therefore candidate genes for GRA. Here we demonstrate complete linkage of GRA in a large kindred to a gene duplication arising from unequal crossing over, fusing the 5' regulatory region of 11 beta-hydroxylase to the coding sequences of aldosterone synthase (maximum lod score 5.23 for complete linkage, odds ratio of 170,000:1). This mutation can account for all the physiological abnormalities of GRA. Our result represents the demonstration of a mutation causing hypertension in otherwise phenotypically normal animals or humans.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYP11B1Humanprimary hyperaldosteronism  IAGP DNA:gene fusion:intron:Cyp11b2 (human)RGD 
CYP11B2Humanprimary hyperaldosteronism  IAGP DNA:gene fusion:intron:Cyp11b1 (human)RGD 
Cyp11b1Ratprimary hyperaldosteronism  ISOCYP11B1 (Homo sapiens)DNA:gene fusion:intron:Cyp11b2 (human)RGD 
Cyp11b1Mouseprimary hyperaldosteronism  ISOCYP11B1 (Homo sapiens)DNA:gene fusion:intron:Cyp11b2 (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp11b1  (cytochrome P450, family 11, subfamily b, polypeptide 1)

Genes (Mus musculus)
Cyp11b1  (cytochrome P450, family 11, subfamily b, polypeptide 1)

Genes (Homo sapiens)
CYP11B1  (cytochrome P450 family 11 subfamily B member 1)
CYP11B2  (cytochrome P450 family 11 subfamily B member 2)


Additional Information