A case of SCNN1A splicing mutation presenting as mild systemic pseudohypoaldosteronism type 1
-
Zelal Ekinci
,
Mehmet Baha Aytac
Abstract
Systemic pseudohypoaldosteronism type 1 (PHA1) is characterized by excessive salt loss from the renal tubulus, colon, sweat and salivary glands. Here we present a case of systemic PHA1 whose genetic analysis revealed a homozygous splicing mutation in intron 4 of SCNN1A (c.684+2 T>A) and discuss with the patient’s phenotype. Previously described systemic PHA cases show varying degrees of severity dependent on the mutation. Most of the SCNN1A gene mutations present with a severe phenotype. The long-term follow-up and phenotype of the two reported cases with splicing mutation of the SCNN1A gene are unknown. Our case, with a new splicing mutation of SCNN1A, presented with a severe phenotype in the neonatal period. Since then she has been well without any hospitalization and respiratory illness. Her requirement for medication also decreased gradually. After early infancy she presented a mild systemic PHA1 phenotype up to the age of 39 months. In conclusion, the mutation in the patient is located at the splicing site and is definitely a new and pathogenic one, and the phenotype of the patient was milder as observed in a patient with missense mutation.
This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120017).
References
1. Kuhnle U. Pseudohypoaldosteronism: mutation found, problem solved? Mol Cell Endocrinol 1997;133:77–80.10.1016/S0303-7207(97)00149-4Suche in Google Scholar
2. Hanukoglu A. Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. J Clin Endocrinol Metab 1991;73:936–44.10.1210/jcem-73-5-936Suche in Google Scholar PubMed
3. Geller DS, Zhang J, Zennaro MC, Vallo-Boado A, Rodriguez-Soriano J, et al. Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for neonatal lethality, and phenotypic expression in adults. J Am Soc Nephrol 2006;17:1429–36.10.1681/ASN.2005111188Suche in Google Scholar PubMed
4. Riepe FG. Clinical and molecular features of type 1 pseudohypoaldosteronism. Horm Res 2009;72:1–9.10.1159/000224334Suche in Google Scholar PubMed
5. Zennaro MC, Hubert EL, Fernandes-Rosa FL. Aldosterone resistance: structural and functional considerations and new perspectives. Mol Cell Endocrinol 2012;350:206–15.10.1016/j.mce.2011.04.023Suche in Google Scholar PubMed
6. The Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff. http://www.hgmd.cf.ac.uk.Suche in Google Scholar
7. Kerem E, Bistritzer T, Hanukoglu A, Hofmann T, Zhou Z, et al. Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism. N Engl J Med 1999;341:156–62.10.1056/NEJM199907153410304Suche in Google Scholar PubMed
8. Azad AK, Rauh R, Vermeulen F, Jaspers M, Korbmacher J, et al. Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. Hum Mutat 2009;30:1093–103.10.1002/humu.21011Suche in Google Scholar PubMed
9. Bonny O, Knoers N, Monnens L, Rossier BC. A novel mutation of the epithelial Na+ channel causes type 1 pseudohypoaldosteronism. Pediatr Nephrol 2002;17:804–8.10.1007/s00467-002-0945-8Suche in Google Scholar PubMed
10. Edelheit O, Hanukoglu I, Gizewska M, Kandemir N, Tenenbaum-Rakover Y, et al. Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism. Clin Endocrinol (Oxf) 2005;62:547–53.10.1111/j.1365-2265.2005.02255.xSuche in Google Scholar PubMed
11. Chang SS, Grunder S, Hanukoglu A, Rösler A, Mathew PM, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet 1996;12:248–53.10.1038/ng0396-248Suche in Google Scholar PubMed
12. Schaedel C, Marthinsen L, Kristoffersson AC, Kornfält R, Nilsson KO, et al. Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel. J Pediatr 1999;135:739–45.10.1016/S0022-3476(99)70094-6Suche in Google Scholar
13. Saxena A, Hanukoglu I, Saxena D, Thompson RJ, Gardiner RM, et al. Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes. J Clin Endocrinol Metab 2002;87:3344–50.10.1210/jcem.87.7.8674Suche in Google Scholar PubMed
14. Mora-Lopez F, Bernal-Quiros M, Lechuga-Sancho AM, Lechuga-Campoy JL, Hernandez-Trujillo N, et al. Novel mutation in the epithelial sodium channel causing type I pseudohypoaldosteronism in a patient misdiagnosed with cystic fibrosis. Eur J Pediatr 2012;171:997–1000.10.1007/s00431-012-1697-5Suche in Google Scholar PubMed
15. Güran T, Değirmenci S, Bulut İK, Say A, Riepe FG, et al. Critical points in the management of pseudohypoaldosteronism type 1. J Clin Res Pediatr Endocrinol 2011;3:98–100.10.4274/jcrpe.v3i2.20Suche in Google Scholar PubMed PubMed Central
16. Silva N, Costa M, Silva A, Sá C, Martins S, et al. A case of systemic pseudohypoaldosteronism with a novel mutation in the SCNN1A gene. Endocrinol Nutr 2013;60:33–6.10.1016/j.endonu.2012.07.002Suche in Google Scholar PubMed
17. Dirlewanger M, Huser D, Zennaro MC, Girardin E, Schild L, et al. A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1. Am J Physiol Endocrinol Metab 2011;301: E467–73.10.1152/ajpendo.00066.2011Suche in Google Scholar PubMed
18. Hanukoglu A, Edelheit O, Shriki Y, Gizewska M, Dascal N, et al. Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes. J Steroid Biochem Mol Biol 2008;111:268–74.10.1016/j.jsbmb.2008.06.013Suche in Google Scholar PubMed
19. Hanukoglu A, Hanukoglu I. Clinical improvement in patients with autosomal recessive pseudohypoaldosteronism and the necessity for salt supplementation. Clin Exp Nephrol 2010; 14:518–9.10.1007/s10157-010-0326-8Suche in Google Scholar PubMed
20. Adachi M, Asakura Y, Muroya K, Tajima T, Fujieda K, et al. Increased Na reabsorption via the Na-Cl cotransporter in autosomal recessive pseudohypoaldosteronism. Clin Exp Nephrol 2010;14:228–32.10.1007/s10157-010-0277-0Suche in Google Scholar PubMed
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