Details of Disease

General Information of Disease (ID: DIS7D44B)

• Disease Name: Bartter syndrome
• Synonyms: Potassium wasting; hypokalemic alkalosis with hypercalciuria; Bartter disease; aldosteronism with hyperplasia of the adrenal cortex; hypokalemic alkalosis; salt-wasting tubulopathy, Henle's loop type; renal tubular normotensive hypokalemic alkalosis with hypercalciuria; Bartter's syndrome; salt-losing tubular disorder, Henle's loop type
• Definition: Bartter syndrome is a group of rare renal tubular disease characterized by impaired salt reabsorption in the thick ascending limb of Henle's loop and clinically by the association of hypokalemic alkalosis, hypercalciuria/nephrocalcinosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II.
• Disease Hierarchy:
  DISZ75RJ: Inherited renal tubular disease
  DIS6SVEE: Syndromic disease
  DISBGF8S: Renal tubular transport disease
  DIS7D44B: Bartter syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0015231
  MESH ID: D001477
  UMLS CUI: C0004775
  MedGen ID: 2172
  Orphanet ID: 112
  SNOMED CT ID: 707742001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CLCNKA	TT823N1	Limited	Genetic Variation	[1]
SLC12A3	TTP362L	Limited	Genetic Variation	[2]
CYP11B1	TTIQUX7	Strong	Genetic Variation	[3]
KCNJ1	TTJ13ST	Strong	Genetic Variation	[4]
KCNJ10	TTG140O	Strong	Genetic Variation	[5]
REN	TTB2MXP	Strong	Altered Expression	[6]
SLC12A1	TTS087L	Strong	Genetic Variation	[7]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AP3B1	OTYTIH5Q	moderate	Genetic Variation	[8]
DCT	OTYVNTBG	moderate	Biomarker	[9]
FGL1	OTT0QHQ1	moderate	Genetic Variation	[8]
HPS1	OTKS5I7T	moderate	Genetic Variation	[8]
ARHGEF25	OT7162TD	Strong	Altered Expression	[10]
BSND	OTYWZWPD	Strong	Genetic Variation	[11]
CLC	OTYMYR85	Strong	Genetic Variation	[12]
CLCN5	OT9YXZSO	Strong	Genetic Variation	[13]
ESPN	OT7Z6LX2	Strong	Biomarker	[14]
MAGED2	OTMEWNSE	Strong	Biomarker	[15]
PPP1R12A	OT4AVU95	Strong	Biomarker	[10]
TRIP13	OTFM3TI9	Strong	Biomarker	[16]

References

• [1] Pharmacovigilance database search discloses ClC-K channels as a novel target of the AT(1) receptor blockers valsartan and olmesartan.Br J Pharmacol. 2017 Jul;174(13):1972-1983. doi: 10.1111/bph.13794. Epub 2017 Apr 26.
• [2] Hypothesis: SLC12A3 Polymorphism modifies thiazide hypersensitivity of antenatal Bartter syndrome to thiazide resistance.Eur J Med Genet. 2012 Feb;55(2):96-8. doi: 10.1016/j.ejmg.2011.12.006. Epub 2011 Dec 30.
• [3] Two novel mutations in CYP11B1 and modeling the consequent alterations of the translated protein in classic congenital adrenal hyperplasia patients.Endocrine. 2013 Aug;44(1):212-9. doi: 10.1007/s12020-012-9861-2. Epub 2013 Jan 24.
• [4] A novel compound heterozygous KCNJ1 gene mutation presenting as late-onset Bartter syndrome: Case report.Medicine (Baltimore). 2019 Aug;98(34):e16738. doi: 10.1097/MD.0000000000016738.
• [5] Renal phenotype in mice lacking the Kir5.1 (Kcnj16) K+ channel subunit contrasts with that observed in SeSAME/EAST syndrome.Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10361-6. doi: 10.1073/pnas.1101400108. Epub 2011 Jun 1.
• [6] Effect of nonsteroidal anti-inflammatory drugs in children with Bartter syndrome.Pediatr Nephrol. 2019 Apr;34(4):679-684. doi: 10.1007/s00467-018-4135-8. Epub 2018 Nov 13.
• [7] A novel SLC12A1 mutation in Bedouin kindred with antenatal Bartter syndrome type I.Ann Hum Genet. 2019 Sep;83(5):361-366. doi: 10.1111/ahg.12317. Epub 2019 Apr 12.
• [8] Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome.J Am Soc Nephrol. 2000 Aug;11(8):1449-1459. doi: 10.1681/ASN.V1181449.
• [9] Bartter's and Gitelman's syndrome.Curr Opin Pediatr. 2017 Apr;29(2):179-186. doi: 10.1097/MOP.0000000000000447.
• [10] Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive patients.J Hypertens. 2014 Feb;32(2):331-8. doi: 10.1097/HJH.0000000000000075.
• [11] Role of zebrafish ClC-K/barttin channels in apical kidney chloride reabsorption.J Physiol. 2019 Aug;597(15):3969-3983. doi: 10.1113/JP278069. Epub 2019 Jul 3.
• [12] Physiological functions of CLC Cl- channels gleaned from human genetic disease and mouse models.Annu Rev Physiol. 2005;67:779-807. doi: 10.1146/annurev.physiol.67.032003.153245.
• [13] Barttin Regulates the Subcellular Localization and Posttranslational Modification of Human Cl(-)/H(+) Antiporter ClC-5.Front Physiol. 2018 Oct 23;9:1490. doi: 10.3389/fphys.2018.01490. eCollection 2018.
• [14] A new autosomal recessive nonsyndromic hearing impairment locus DFNB96 on chromosome 1p36.31-p36.13.J Hum Genet. 2011 Dec;56(12):866-8. doi: 10.1038/jhg.2011.110. Epub 2011 Sep 22.
• [15] MAGED2: a novel form of antenatal Bartter's syndrome.Curr Opin Nephrol Hypertens. 2018 Jul;27(4):323-328. doi: 10.1097/MNH.0000000000000422.
• [16] Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies.Neurology. 2010 Oct 19;75(16):1459-64. doi: 10.1212/WNL.0b013e3181f88173.