A novel epithelial sodium channel ?-subunit mutation associated with hypertensive Liddle syndrome

Abstract

Low-renin hypertension responsive to amiloride-thiazide therapy in a 4-year-old Afro-Haitian girl suggested Liddle syndrome. Urine steroid profiling substantiated the diagnosis and DNA analysis of the epithelial sodium channel (ENaC) revealed a novel heterozygous beta ENaC mutation in the patient and in her hypertensive father. Liddle syndrome should be considered as a cause of hypertension in young children particularly with suppressed renin activity.

Liddle syndrome in a Serbian family and literature review of underlying mutations

“…Early diagnosis and appropriately tailored treatment should avoid the complications of long-term unrecognized or inappropriately managed HT. Genetic counseling is indicated if one of the parents is affected in order to target continued surveillance of at-risk subjects at an early age [8,44].…”

“…However, the proband was less responsive to amiloride/ hydrochlorothiazide treatment compared to his mother, requiring two times larger drug dosages to achieve stable BP control. Although this drug combination was occasionally given in Liddle syndrome patients [8], the drug of choice is an ENaC blocking agent, amiloride or triamterene associated with a low salt diet, which is usually adequate to control HT [47]. In our country, amiloride is unavailable as a single drug but only in the fixed combination with hydrochlorothiazide, the amount of which is excessive compared to that of amiloride.…”

“…These genetic defects either delete the C terminus of beta or gamma ENaC [11,36] or mutate a proline or a tyrosine within a short sequence, called PY (Pro-Pro-x-Tyr) motif [8,27,28] (Table 2). The PY motif, or extended PY motif (PPx-YxxL) [37], is highly conserved in the C termini of all ENaC subunits and serves as binding site for Nedd 4-2, an E3 ubiquitin ligase [38].…”

“…Here, the patient showed a normal 46, XY karyotype. Mutational analysis of ENaC subunit genes SCNN1B and SCNN1G was performed in the index case as previously reported [8]. Subsequently, the respective SCNN1B PCR product was analyzed in the family members.…”

Epithelial Sodium Channel

“…New families or sporadic cases have confirmed the critical importance of the C terminus of either ␤-or ␥-subunit. [7][8][9][10][11][12][13][14][15] A point mutation in the extracellular domain of the ENaC ␥-subunit has been identified in 1 sporadic case in Finland. 16 This Asn530Ser mutation is located in a critical region that controls channel gating.…”