Screening for genetic causes of hypertension.
Monogenic or single-gene forms of human hypertension result from mutations involving regulatory elements of the renin-angiotensin-aldosterone system (RAAS) or occur in syndromes associated with hereditary pheochromocytoma. RAAS gain-of-function mutations result in sodium retention, suppression of plasma renin activity, and often, but not invariably, hypokalemia. Hereditary RAAS syndromes result from intrinsic renal abnormalities (apparent mineralocorticoid excess and Liddle's syndromes) or from mineralocorticoid excess states (congenital adrenal hyperplasia and glucocorticoid-remediable aldosteronism). In the hereditary pheochromocytoma syndromes many asymptomatic individuals are identified because they are at-risk individuals in kindreds with a pheochromocytoma-predisposing syndrome. On the other hand, up to 25% of subjects with presumed "sporadic" pheochromocytoma have germline mutations in one of four pheochromocytoma susceptibility genes (the RET proto-oncogene, von Hippel-Lindau gene, neurofibromatosis F1 gene, and succinate dehydrogenase subunit D and succinate dehydrogenase subunit B genes). Hereditary pheochromocytomas are typically intra-adrenal and bilateral and patients typically present at younger ages compared with sporadic pheochromocytoma.
Dluhy
Robert G
RG
Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. RDluhy@Partners.org
D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D006973:Hypertension / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics; D000090063:Proto-Oncogene Mas; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000235:genetics; D013577:Syndrome
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012083:Renin