ABSTRACT
BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is a rare genetic disorder manifested by hyperkalemia and early hypertension. Hypercalciuria is another accompanying feature. Mutations in WNK4 and WNK1 were found initially, and recently additional mutations were found in two genes, KLHL3 and CUL3, which are components of the Ubiquitin system. It was not reported whether these latter mutations are accompanied by hypercalciuria. METHODS: We compared urinary calcium excretion (UCa) in affected subjects with FHHt and KLHL3 mutations, and in their unaffected family members, and in affected subjects with FHHt and WNK4 Q565E mutation. RESULTS: Two new families with FHHt including a total number of 23 subjects, 10 of them affected, in whom previously described mutations in KLHL3 (Q309R and R528H) were identified. Presenting features were short stature in the first family, and transient tachypnea of the newborn (TTN) in the second. Affected subjects had hypercalciuria. UCa levels in affected subjects in the two families were significantly higher than in unaffected subjects (0.608 ± 0.196 vs. 0.236 ± 0.053 mmol Ca per mmol creatinine, respectively (p < 0.0001)). Hypercalciuria in FHHt with KLHL3 mutations is less severe than that observed in FHHt with the Q565E WNK4 mutation (0.608 ± 0.196 (n = 10) mmol Ca per mmol creatinine versus 0.860 ± 0.295 (n = 29), respectively (p = 0.0168)). CONCLUSIONS: FHHt caused by KLHL3 mutations is accompanied by hypercalciuria as well as hyperkalemia and hypertension. The similar phenomena observed for FHHt caused by WNK4 mutations fits the other evidence that WNK4 mutations are activating, and the aberrant mechanism of calcium handling by the kidney in FHHt.
Subject(s)
Carrier Proteins/genetics , Hypercalciuria/etiology , Hypercalciuria/genetics , Pseudohypoaldosteronism/complications , Pseudohypoaldosteronism/genetics , Adaptor Proteins, Signal Transducing , Aged , Arabs , Blood Pressure/physiology , Body Height , Calcium/urine , Child , Creatinine/blood , Female , Humans , Kidney Function Tests , Male , Microfilament Proteins , Middle Aged , Mutation/genetics , Pedigree , Transient Tachypnea of the Newborn/genetics , Twins, MonozygoticABSTRACT
OBJECTIVE: The aim of this study was to investigate whether there is a role of the serum glucocorticoid kinase (SGK) 1 gene, which has an effect on the control of the epithelial sodium channels. MATERIALS AND METHOD: This study included patients who were diagnosed with transient tachypnea of the newborn (TTN) with more than 37 weeks of gestation. As the control group, healthy newborns of the same gestational age were included. From each group, within the first 5 d of their lives, 2 cc of whole blood was taken in EDTA tubes, and stored at -80 °C. The DNA extraction was performed. RESULTS: There were 32 patients in the TTN, and also 32 patients in the control group. The heterozygous allele rs1057293 (3/28) and rs1743966 (8/28) were located in the encoder region of the SGK 1 gene. In addition, in encoding region of the SGK 1 gene, the Arg97Ile (1/28), which causes the amino acid changes, had a genotype frequency of 0.0357, and a mutation was identified in Arg97Ile. DISCUSSION: We have defined polymorphisms rs1057293 and rs1743966 in the SGK 1 gene, and the Arg97Ile mutation, for the first time in patients with TTN. This pilot study gave us some clues about a genetic basis of TTN phenotype, next to the lack of the pulmonary maturation.
Subject(s)
Immediate-Early Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Transient Tachypnea of the Newborn/genetics , Birth Weight/genetics , Birth Weight/physiology , Case-Control Studies , DNA Mutational Analysis , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Gestational Age , Humans , Infant, Newborn , Male , Mutation, Missense/physiology , Pilot Projects , Polymorphism, Single Nucleotide/physiologyABSTRACT
BACKGROUND: Transient tachypnea of neonate (TTN) and respiratory distress syndrome (RDS) of the newborn are the most common cause of early respiratory distress in the immediate neonatal period. There is increasing evidence to support the role for the activation of the renin angiotensin system during acute lung injury. OBJECTIVES: The purpose of this study was to determine if there is a relationship between angiotensin-converting enzyme (ACE) I/D polymorphism, ACE activity and TTN and respiratory distress syndromes. METHODS: Nineteen neonates with TTN, 20 neonates with RDS and 21 control infants are studied for ACE polymorphism and serum ACE activity. RESULTS: Twenty six (43.3%) patients have DD polymorphism, 19 (31.7%) patients have ID polymorphism and 15 (25%) patients have II polymorphism. Serum ACE activity is 43.5 ± 1.8 (40-46) U/L in DD, 31.5 ± 2.3 (28-36) U/L in ID and 22.1 ± 2.1(19-46) U/L in II patient. CONCLUSIONS: The study could not find any difference in DD alleles and ACE activity between control group and TTN group. ACE polymorphism was not different between RDS group and control group in this study.
