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Abstract: FR-PO580

Familiar Hyperkalemic Hypertension Genotype with a Negative Phenotype: A CUL3 Mosaicism

Session Information

Category: Trainee Case Report

  • 902 Fluid and Electrolytes: Clinical


  • Ostrosky-Frid, Mauricio, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
  • Chavez-Canales, Maria, Instituto de Investigaciones Biomedicas, UNAM, Mexico City, Mexico
  • Simsolo, Rosa B., Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina
  • Romo, Miriam A., Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina
  • Gamba, Gerardo, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico

The Familiar Hyperkalemic Hypertension (FHHt) is an inherited disease featuring arterial hypertension with hyperkalemia, metabolic acidosis, and hypercalciuria, that is mainly due to overactivation of the thiazide-sensitive renal NaCl cotransporter in the distal convoluted tubule, as a consequence of mutations in four different genes: two encoding the kinases known as WNK1 and WNK4 and two encoding proteins that are components of a Ring type ubiquitin ligase complex, known as KLHL3 and CUL3. Mutations in CUL3 produce the more severe phenotype that in all 36 reported cases result in a shorter protein due to skipping of exon 9 and has been described as de novo mutation or as autosomal dominant inherited from one parent.

Case Description

Here we report on a 12 year-old boy with arterial hypertension (150/100mmHg), hyperkalemia (7 mEq/L) metabolic acidosis (pH 7.0; HCO3- 17.8 mEq/L) and hyperchloremia (108 mEq/L). Two months after hydrochlorothiazide was initiated the blood pressure was 129/76 and serum electrolyte values were normal (K+, 4.5 mEq/L; Cl- 98 mEq/L, pH 7.37 and HCO3- 25.8 mEq/L). DNA from the proband and his parents were obtained with their consent to evaluate the cause of the FHHt. The proband’s DNA analysis revealed a CUL3 mutation resulting in exon 9 deletion. The mutation was present in the mother’s blood DNA, but not in the father’s. The mother, however, exhibits no FHHt phenotype. Her blood pressure and serum electrolytes were normal. The CUL3 mutation was found in DNA extracted from the mother’s oral mucosa but at lower levels than in the blood. The mother of the proband is a unique occurrence of CUL3 FHHt genotype, with no phenotype, due to a mosaicism.


Mosaicism refers to the presence of two genetically distinct cells lines with distinct karyotype or genotype in the same individual and results from postzygotic mutational events. Individuals may present gonadal mosaicism (found only in the gametes), somatic mosaicism, or a combination of both. In somatic mosaicism, it is frequent to find different proportions of the two cell lines across tissues, even within the same embryonic lineage (ectoderm, endoderm or mesoderm). In the proband's mother, the mutation exhibits presumably little to no effect on renal tubular cells, but is present in the oocytes and was inherited by her child.