title: Structural chromosome disruption of the NR3C2 gene causing pseudohypoaldosteronism type 1 presenting in infancy.
abstract: Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance presenting in infancy with renal salt wasting and failure to thrive. Here, we present the case of a 6-week-old baby girl who presented with mild hyponatraemia and dehydration with a background of severe failure to thrive. At presentation, urinary sodium was not measurably increased, but plasma aldosterone and renin were increased, and continued to rise during the subsequent week. Despite high calorie feeds the infant weight gain and hyponatraemia did not improve until salt supplements were commenced. Subsequently, the karyotype was reported as 46,XX,inv (4)(q31.2q35). A search of the OMIM database for related genes at or near the inversion breakpoints, showed that the mineralocorticoid receptor gene (NR3C2) at 4q31.23 was a likely candidate. Further FISH analysis showed findings consistent with disruption of the NR3C2 gene by the proximal breakpoint (4q31.23) of the inversion. There was no evidence of deletion or duplication at or near the breakpoint. This is the first report of a structural chromosome disruption of the NR3C2 gene giving rise to the classical clinical manifestations of pseudohypoaldosteronism type 1 in an infant.
authors.affiliation: Department of Endocrinology, Princess Margaret Hospital for Children, Perth, Western Australia, Australia. SusanMary.O'Connell@health.wa.gov.au
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Connell
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Johnson
authors.forename: Barry D
authors.initials: BD
authors.lastname: Lewis
authors.forename: Louise
authors.initials: L
authors.lastname: Staltari
authors.forename: Joanne
authors.initials: J
authors.lastname: Peverall
authors.forename: Trang
authors.initials: T
authors.lastname: Ly
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Martin
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Jones
authors.forename: Glynis J
authors.initials: GJ
authors.lastname: Price
authors.forename: Ashleigh
authors.initials: A
authors.lastname: Murch
authors.forename: Catherine S Y
authors.initials: CS
authors.lastname: Choong
mesh_terms: D007446:Chromosome Inversion; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D019587:Dietary Supplements; D005183:Failure to Thrive / Q000209:etiology*; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000209:etiology; D007223:Infant; D011546:Pseudohypoaldosteronism / Q000097:blood / Q000151:congenital* / Q000178:diet therapy / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D012965:Sodium Chloride / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C561839:NR3C2 protein, human; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D012965:Sodium Chloride