Mixed Bartter-Gitelman syndrome: an inbred family with a heterogeneous phenotype expression of a novel variant in the CLCNKB gene

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• 作者：Amar Al-Shibli ; Madinah Yusuf ; Issam Abounajab ; Patrick J Willems
• 关键词：Bartter syndrome ; Gitelman syndrome ; Mutation ; Phenotype ; CLCNKB gene
• 刊名：SpringerPlus
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：3
• 期：1
• 全文大小：480KB
• 参考文献：Amirlak I, Dawson K: Bartter syndrome: an overview. Q J Med 2000, 93:207鈥?15.CrossRef
  Briet M, Vargas-Poussou R, Lourdel S, Houillier P, Blanchard A: How Bartter's and Gitelman's syndromes, and Dent's disease have provided important insights into the function of three renal chloride channels: ClC-Ka/b and ClC-5. Nephron Physiol 2006, 103:7鈥?3.CrossRef
  Brochard K, Boyer O, Blanchard A: Phenotype- genotype correlation in antenatal and neonatal variant of Bartter syndrome. Nephrol Dial Transplant 2009, 24:1455鈥?464.CrossRef
  Coto E, Rodriguez Jeck N, Alvarez V, Stone R, Loris C, Rodriguez M, Fischbach M, Seyberth W, Santos F: A new mutation (intron 9 +1聽G鈥?gt;鈥塗) in the SLC12A3 gene is linked to Gitelman syndrome in Gypsies. Kidney Int 2004, 65:25鈥?9.CrossRef
  Cruz AJ, Castro A: Gitelman or Bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation. BMJ Case Rep 2013, 22:2013.
  Dong Yan JI, Gang FQ, Xianting Z, Gengru JIANG: A novel splicing mutation in CLCNKB in a Chinese patient with Bartter syndrome type III. Chin Med J 2010,123(21):3151鈥?153.
  Enriquez R, Adam V, Sirvent AE, Garc铆a-Garc铆a AB, Mill谩n I, Amor贸s F: Gitelman syndrome due to p.A204T mutation in CLCNKB gene. IntUrolNephrol 2010,42(4):1099鈥?102.
  Fain PR, McFann KK, Taylor M, et al.: Modifier genes play a significant role in the phenotypic expression of PKD1. Kidney Int 2005, 67:1256鈥?267.CrossRef
  Fukuyama S, Okudaira S, Yamazato S, Yamazato M, Ohta T: Analysis of renal tubular electrolyte trans- porter genes in seven patients with hypokalemic metabolic alkalosis. Kidney Int 2003, 64:808鈥?16.CrossRef
  Fukuyama S, Hiramatsu M, Akagi M, Higa M, Ohta T: Novel mutations of the chloride channel Kb gene in two Japanese patients clinically diagnosed as Bartter syndrome with hypocalciuria. J Clin Endocrinol Metab 2004, 89:5847鈥?850.CrossRef
  Gorgojo JJ, Donnay S, Jeck N, Konrad M: A Spanish founder mutation in the chloride channel gene, CLCNKB , as a cause of atypical Bartter syndrome in adult age. Horm Res 2006,65(2):62鈥?8.CrossRef
  Israel Z, Raymonde , Ali H, Valentina L, Ihab H, Nadine C, Farid N: A novel mutation in the chloride channel gene, CLCNKB , as a cause of Gitelman and Bartter syndromes. Kidney Int 2003, 63:24鈥?2.CrossRef
  Jeck N, Konrad M, Peters M, Weber S, Bonzel KE, Seyberth HW: Mutations in the chloride channel gene, CLCNKB, leading to a mixed Bartter-Gitelman phenotype. Pediatr Res 2000, 48:754鈥?58.CrossRef
  Jeck N, Waldegger P, Doroszewicz J, Seyberth H, Waldegger S: A common sequence variation of the CLCNKB gene strongly activates ClC- Kb chloride channel activity. Kidney Int 2004,65(1):190鈥?97.CrossRef
  Konrad M, Weber S: Recent Advances in Molecular Genetics of Hereditary Magnesium-Losing Disorders. J Am Soc Nephrol 2003, 14:249鈥?60.CrossRef
  Konrad M, Vollmer M, Lemmink HH, et al.: Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome. J Am Soc Nephrol 2000,11(8):1449鈥?459.
  Lee BH, Cho HY, Lee H, et al.: Genetic basis of Bartter syndrome in Korea. Nephrol Dial Transplant 2012,27(4):1516鈥?521.CrossRef
  Naesens M, Steels P, Verberckmoes R, Vanrenterghem Y, Kuypers D: Bartter's and Gitelman's syndromes: from gene to clinic. Nephron Physiol 2004,96(3):65鈥?8.CrossRef
  Nozu K, Fu XJ, Nakanishi K, Yoshikawa N, Kaito H, Kanda K, Krol RP, Miyashita R, Kamitsuji H, Kanda S, Hayashi Y, Satomura K, Shimizu N, Iijima K, Matsuo M: Molecular analysis of patients with type III Bartter syndrome: picking up large heterozygous deletions with semiquantitative PCR. Pediatr Res 2007,62(3):364鈥?69.CrossRef
  Peters M, Jeck N, Reinalter S, Leonhardt A, Tonshoff B, Klaus GG, Konrad M, Seyberth HW: Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med 2002,112(3):183鈥?90.CrossRef
  Pierre Robitaille AM, Ning H, York P: Bartter syndrome in two sisters with a novel mutation of the CLCNKB gene, one with deafness. ur J Pediatr 2011, 170:1209鈥?211.
  Rodriguez J, Vallo A, Perez G: A founder variant in the CLCNKB gene causes Bartter syndrome type III in Spain. Pediatr Nephrol 2005,20(7):891鈥?96.CrossRef
  Seyberth HW: An improved terminology and classification of Bartter-like syndromes. Nat Clin Pract Nephrol 2008,4(10):560鈥?67.CrossRef
  Seyberth HW, Schlingmann KP: Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects. Pediatr Nephrol 2011,26(10):1789鈥?802.CrossRef
  Toshihiro T, Mitsuru N, Yutaka T, Yumiko M, Shigetaka S, Masaaki Y, Mutsumi M, Masanori A, Katsuhiko T, Hiroshi M: Molecular Analysis of the CLCNKB Gene in Japanese Patients with Classic Bartter Syndrome. Endocrine Journal 2006,53(5):647鈥?52.CrossRef
  Uchida S: In vivo role of CLC chloride channels in the kidney. Am J Physiol Renal Physiol 2000, 279:F802-F808.
  Urbanova M, Reiterova J, 艩tekrova J, Lnenicka P, Rysava R: DNA Analysis of Renal Electrolyte Transporter Genes Among Patients Suffering from Bartter and Gitelman Syndromes 鈥?Summary of Mutation Screening. Folia Biol (Praha) 2011, 57:65鈥?3.
  Vargas R, Dahan K, Kahila D, Venisse A, Riveira E, Debaix H, Grisart B, Bridoux F, Unwin R, Moulin B, Haymann JP, Vantyghem MC, Rigothier C, Dussol B, Godin M, Nivet H, Dubourg L, Tack I, Gimenez AP, Houillier P, Blanchard A, Devuyst O, Jeunemaitre X: Spectrum of mutations in Gitelman syndrome. J Am Soc Nephrol 2011,22(4):693鈥?03.CrossRef
  Xiumin W, Zheng S, Meichun X, Junfen F, Li L: A Chinese Girl with Bartter Syndrome Type III due to a Novel Mutation and/or Single Nucleotide Polymorphisms (SNPs) in CLCNKB Gene. Iran J Pediatr 2013,23(1):89鈥?4.
  Yu Y, Xu C, Pan X, et al.: Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome. Clin Genet 2010,77(2):155鈥?62.CrossRef
  Zelikovic I, Szargel R, Hawash A, Labay V, Hatib I, Cohen N, Nakhoul F: A novel mutation in the chloride channel gene, CLCNKB , as a cause of Gitelman and Bartter syndromes. Kidney Int 2003,63(24鈥?2):647鈥?52.
  
• 作者单位：Amar Al-Shibli (5)
  Madinah Yusuf (4)
  Issam Abounajab (5)
  Patrick J Willems (5)
  
  5. GENDIA (GENetic DIAgnostic Network), Antwerp, Belgium
  4. Department of Academic Affairs, Tawam Hospital, Al-Ain, United Arab Emirates
  
• 刊物类别：Science, general;
• 刊物主题：Science, general;
• 出版者：Springer International Publishing
• ISSN：2193-1801

文摘

Patients with renal diseases associated with salt-losing tubulopathies categorized as Gitelman and classic form of Bartter syndrome have undergone genetic screening for possible mutation capture in two different genes: SLC12A3 and CLCNKB. Clinical symptoms of these two diseases may overlap. Bartter syndrome and Gitelman syndrome are autosomal recessive salt-losing tubulopathies with hypokalemia, metabolic alkalosis, hyperreninemia, hyperplasia of the juxtaglomerular apparatus, hyperaldosteronism, and, in some patients, hypomagnesemia. Here we describe four patients from an inbred family with a novel missense variant in the CLCNKB gene. All of patients are asymptomatic; yet they have the typical metabolic abnormality of salt losing tubulopathies. One of those patients had hypomagnesaemia while others not. Clinical and laboratory data of all patients was described. All 4 patients have a homozygous c.490G鈥?gt;鈥塗 missense variant in exon 5 of the CLCNKB gene. This variant alters a glycine into a cysteine on amino acid position 164 of the resulting protein (p.Gly164Cys). The c.490G鈥?gt;鈥塗 variant is a novel variant not previously described in other patients nor controls. Polyphen analysis predicts the variation to be possibly damaging. Analysis of SLC12A3 was normal. Here in we are describing a novel homozygous c.490G鈥?gt;鈥塗 missense variation was identified in exon 5 of the CLCNKB gene was identified in an Emirati patients with a mild manifestation of Bartter - Gitelman syndrome. Keywords Bartter syndrome Gitelman syndrome Mutation Phenotype CLCNKB gene