iBet uBet web content aggregator. Adding the entire web to your favor.
Link to original content: http://omim.org/entry/613090
ORPHA: 112, 89938; DO: 0110146;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p36.13 | Bartter syndrome, type 4b, digenic | 613090 | Digenic recessive | 3 | CLCNKA | 602024 |
| 1p36.13 | Bartter syndrome, type 4b, digenic | 613090 | Digenic recessive | 3 | CLCNKB | 602023 |
A number sign (#) is used with this entry because neonatal Bartter syndrome type 4B with sensorineural deafness (BARTS4B) is caused by simultaneous mutation in both the CLCNKA (602024) and CLCNKB (602023) genes.
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997).
Patients with antenatal (or neonatal) forms of Bartter syndrome (e.g., BARTS1, 601678) typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012).
For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
In a child with renal salt wasting and deafness who had no mutation in the BSND gene (606412), Schlingmann et al. (2004) identified both a homozygous deletion of the CLCNKB gene (602023.0008) and a homozygous trp80-to-cys mutation in the CLCNKA gene (W80C; 602024.0001). The patient was born prematurely to consanguineous parents, and the pregnancy was complicated by severe maternal polyhydramnios during the last 6 weeks of gestation. Because this combined impairment of the CLCNKA and CLCNKB genes resulted in a phenotype mimicking that caused by defects in barttin, Schlingmann et al. (2004) concluded that this case supported the notion that the CLCNK-type channels are regulated by barttin and offered strong evidence of genetic heterogeneity in patients who have both severe renal salt wasting and deafness.
Nozu et al. (2008) reported a 2-year-old Japanese girl with a severe form of Bartter syndrome and sensorineural deafness who was born of nonconsanguineous parents. Genetic analysis showed 2 heterozygous mutations in the CLCNKA (602024.0002) and CLCNKB (602023.0011) genes on the paternal allele, and a 12-kb deletion involving portions of the CLCNKA and CLCNKB genes on the maternal allele. Neither parent was clinically affected. The findings indicated clear digenic inheritance in this patient and confirmed that loss of function of all 4 alleles of the CLCNKA and CLCNKB genes can result in Bartter syndrome type 4B.
Fremont, O. T., Chan, J. C. M. Understanding Bartter syndrome and Gitelman syndrome. World J. Pediat. 8: 25-30, 2012. [PubMed: 22282380] [Full Text: https://doi.org/10.1007/s12519-012-0333-9]
Nozu, K., Inagaki, T., Fu, X. J., Nozu, Y., Kaito, H., Kanda, K., Sekine, T., Igarashi, T., Nakanishi, K., Yoshikawa, N., Iijima, K., Matsuo, M. Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness. J. Med. Genet. 45: 182-186, 2008. [PubMed: 18310267] [Full Text: https://doi.org/10.1136/jmg.2007.052944]
Schlingmann, K. P., Konrad, M., Jeck, N., Waldegger, P., Reinalter, S. C., Holder, M., Seyberth, H. W., Waldegger, S. Salt wasting and deafness resulting from mutations in two chloride channels. New Eng. J. Med. 350: 1314-1319, 2004. [PubMed: 15044642] [Full Text: https://doi.org/10.1056/NEJMoa032843]
Simon, D. B., Bindra, R. S., Mansfield, T. A., Nelson-Williams, C., Mendonca, E., Stone, R., Schurman, S., Nayir, A., Alpay, H., Bakkaloglu, A., Rodriguez-Soriano, J., Morales, J. M., Sanjad, S. A., Taylor, C. M., Pilz, D., Brem, A., Trachtman, H., Griswold, W., Richard, G. A., John, E., Lifton, R. P. Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. Nature Genet. 17: 171-178, 1997. [PubMed: 9326936] [Full Text: https://doi.org/10.1038/ng1097-171]
Simon, D. B., Karet, F. E., Rodriguez-Soriano, J., Hamdan, J. H., DiPietro, A., Trachtman, H., Sanjad, S. A. Lifton, R. P.: Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK. Nature Genet. 14: 152-156, 1996. [PubMed: 8841184] [Full Text: https://doi.org/10.1038/ng1096-152]