Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4 mutations in pendred syndrome/enlarged vestibular aqueducts

BMC Medical Genetics

Maria Bitner-Glindzicz¹  Lucy Jenkins³  Kaukab Rajput²  Ann-Marie Differ³  Priya Landa³ 

[1] Clinical and Molecular Genetics Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK;Cochlear Implant Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK;North East Thames Regional Genetics Service Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, 37 Queen Square,York House, London WC1N 3BH, UK

关键词: SLC26A4;    Pendred syndrome;    KCNJ10;    Hearing impairment;    FOXI1;    EVAS;    Epilepsy;    Enlarged vestibular aqueducts;    Deafness;   

Others  :  1127649
DOI  :  10.1186/1471-2350-14-85

 received in 2013-01-02, accepted in 2013-08-06,  发布年份 2013

【 摘 要 】

Background

Pendred syndrome is a common autosomal recessive disorder causing deafness. Features include sensorineural hearing impairment, goitre, enlarged vestibular aqueducts (EVA) and occasionally Mondini dysplasia. Hearing impairment and EVA may occur in the absence of goitre or thyroid dyshormonogensis in a condition known as non-syndromic EVA. A significant number of patients with Pendred syndrome and non-syndromic EVA show only one mutation in SLC26A4. Two genes, KCNJ10, encoding an inwardly rectifying potassium channel and FOXI1, a transcriptional factor gene, are thought to play a role in the disease phenotypes.

Methods

Using Polymerase Chain Reaction and Sanger sequencing, sixty-eight patients with monoallelic mutations of SLC26A4 were tested for mutations in KCNJ10 and FOXI1.

Results

Two variants were observed in the KCNJ10 gene, p.Arg271Cys in three patients and p.Arg18Gln in one patient; only one variant, p.Arg123Trp was observed in the FOXI1 gene in a single patient. Both p.Arg271Cys and p.Arg18Gln are likely to be polymorphisms as judged by their frequency in the general population.

Conclusion

Therefore we found no evidence for a significant association between mutations of KCNJ10 and FOXI1 with SLC26A4. It was also observed that the variant, p.Arg271Cys in KCNJ10, previously thought to have a protective effect against seizure susceptibility, was found in a patient with Pendred syndrome with co-existing epilepsy.

【 授权许可】

   
2013 Landa et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Fraser GR: Association of congenital deafness with goitre (Pendred’s syndrome). Ann Hum Genet 1965, 28:201-248.
• [2]Kopp P, Pesce L, Solis-S JC: Pendred syndrome and iodide transport in the thyroid. Trends Endocrinol Metab 2008, 19(7):260-268.
• [3]Pendred V: Deaf-mutism and goitre. 1896, 2:532.
• [4]Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, et al.: Molecular analysis of the PDS gene in Pendred syndrome. Hum Mol Genet 1998, 7(7):1105-1112.
• [5]Bizhanova A, Kopp P: Genetics and phenomics of Pendred syndrome. Mol Cell Endocrinol 2010, 322(1–2):83-90.
• [6]Phelps PD, Coffey RA, Trembath RC, Luxon LM, Grossman AB, Britton KE, et al.: Radiological malformations of the ear in Pendred syndrome. Clin Radiol 1998, 53(4):268-273.
• [7]Yang JJ, Tsai CC, Hsu HM, Shiao JY, Su CC, Li SY: Hearing loss associated with enlarged vestibular aqueduct and Mondini dysplasia is caused by splice-site mutation in the PDS gene. Hear Res 2005, 199(1–2):22-30.
• [8]Joshua B, Kaplan DM, Raveh E, Lotan D, Anikster Y: Audiometric and imaging characteristics of distal renal tubular acidosis and deafness. J Laryngol Otol 2008, 122(2):193-198.
• [9]Pryor SP, Madeo AC, Reynolds JC, Sarlis NJ, Arnos KS, Nance WE, et al.: SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities. J Med Genet 2005, 42(2):159-165.
• [10]Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, et al.: Pendrin: an apical Cl-/OH-/. Am J Physiol Renal Physiol 2001, 280(2):F356-F364.
• [11]Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP: The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999, 21(4):440-443.
• [12]TROTTER WR: The association of deafness with thyroid dysfunction. Br Med Bull 1960, 16:92-98.
• [13]Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE, et al.: Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat 2001, 17(5):403-411.
• [14]Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, et al.: Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997, 17(4):411-422.
• [15]Coucke P, Van CG, Demirhan O, Kabakkaya Y, Balemans W, Van HP, et al.: The gene for Pendred syndrome is located between D7S501 and D7S692 in a 1.7-cM region on chromosome 7q. Genomics 1997, 40(1):48-54.
• [16]Dai P, Stewart AK, Chebib F, Hsu A, Rozenfeld J, Huang D, et al.: Distinct and novel SLC26A4/Pendrin mutations in Chinese and U.S. patients with nonsyndromic hearing loss. Physiol Genomics 2009, 38(3):281-290.
• [17]Li XC, Everett LA, Lalwani AK, Desmukh D, Friedman TB, Green ED, et al.: A mutation in PDS causes non-syndromic recessive deafness. Nat Genet 1998, 18(3):215-217.
• [18]Glaser B: Pendred syndrome. Pediatr Endocrinol Rev 2003, 1(Suppl 2):199-204.
• [19]Yang T, Vidarsson H, Rodrigo-Blomqvist S, Rosengren SS, Enerback S, Smith RJ: Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4). Am J Hum Genet 2007, 80(6):1055-1063.
• [20]Azaiez H, Yang T, Prasad S, Sorensen JL, Nishimura CJ, Kimberling WJ, et al.: Genotype-phenotype correlations for SLC26A4-related deafness. Hum Genet 2007, 122(5):451-457.
• [21]Yang T, Gurrola JG, Wu H, Chiu SM, Wangemann P, Snyder PM, et al.: Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome. Am J Hum Genet 2009, 84(5):651-657.
• [22]Shang L, Lucchese CJ, Haider S, Tucker SJ: Functional characterisation of missense variations in the Kir4.1 potassium channel (KCNJ10) associated with seizure susceptibility. Brain Res Mol Brain Res 2005, 139(1):178-183.
• [23]Hibino H, Horio Y, Inanobe A, Doi K, Ito M, Yamada M, et al.: An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4. 1), in cochlear stria vascularis of inner ear: its specific subcellular localization and correlation with the formation of endocochlear potential. J Neurosci 1997, 17(12):4711-4721.
• [24]Reimann F, Ashcroft FM: Inwardly rectifying potassium channels. Curr Opin Cell Biol 1999, 11(4):503-508.
• [25]Wangemann P, Nakaya K, Wu T, Maganti RJ, Itza EM, Sanneman JD, et al.: Loss of cochlear HCO3-secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model. Am J Physiol Renal Physiol 2007, 292(5):F1345-F1353.
• [26]Wangemann P, Itza EM, Albrecht B, Wu T, Jabba SV, Maganti RJ, et al.: Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model. BMC Med 2004, 2:30. BioMed Central Full Text
• [27]Ferraro TN, Golden GT, Smith GG, Martin JF, Lohoff FW, Gieringer TA, et al.: Fine mapping of a seizure susceptibility locus on mouse chromosome 1: nomination of Kcnj10 as a causative gene. Mamm Genome 2004, 15(4):239-251.
• [28]Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, et al.: Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 2009, 360(19):1960-1970.
• [29]Hulander M, Kiernan AE, Blomqvist SR, Carlsson P, Samuelsson EJ, Johansson BR, et al.: Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice. Development 2003, 130(9):2013-2025.
• [30]Vidarsson H, Westergren R, Heglind M, Blomqvist SR, Breton S, Enerback S: The forkhead transcription factor Foxi1 is a master regulator of vacuolar H-ATPase proton pump subunits in the inner ear, kidney and epididymis. PLoS One 2009, 4(2):e4471.
• [31]Lenzen KP, Heils A, Lorenz S, Hempelmann A, Hofels S, Lohoff FW, et al.: Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy. Epilepsy Res 2005, 63(2–3):113-118.
• [32]Buono RJ, Lohoff FW, Sander T, Sperling MR, O’Connor MJ, Dlugos DJ, et al.: Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res 2004, 58(2–3):175-183.
• [33]Sicca F, Imbrici P, D′Adamo MC, Moro F, Bonatti F, Brovedani P, et al.: Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K + channel Kir4.1. Neurobiol Dis 2011, 43(1):239-247.
• [34]Chen K, Wang X, Sun L, Jiang H: Screening of SLC26A4, FOXI1, KCNJ10, and GJB2 in bilateral deafness patients with inner ear malformation. Otolaryngol Head Neck Surg 2012, 146(6):972-978.
• [35]Mercer S, Mutton P, Dahl HH: Identification of SLC26A4 mutations in patients with hearing loss and enlarged vestibular aqueduct using high-resolution melting curve analysis. Genet Test Mol Biomarkers 2011, 15(5):365-368.
• [36]Jonard L, Niasme-Grare M, Bonnet C, Feldmann D, Rouillon I, Loundon N, et al.: Screening of SLC26A4, FOXI1 and KCNJ10 genes in unilateral hearing impairment with ipsilateral enlarged vestibular aqueduct. Int J Pediatr Otorhinolaryngol 2010, 74(9):1049-1053.
• [37]Wu CC, Lu YC, Chen PJ, Yeh PL, Su YN, Hwu WL, et al.: Phenotypic analyses and mutation screening of the SLC26A4 and FOXI1 genes in 101 Taiwanese families with bilateral nonsyndromic enlarged vestibular aqueduct (DFNB4) or Pendred syndrome. Audiol Neurootol 2010, 15(1):57-66.
• [38]Cirello V, Bazzini C, Vezzoli V, Muzza M, Rodighiero S, Castorina P, et al.: Molecular and functional studies of 4 candidate loci in Pendred syndrome and nonsyndromic hearing loss. Mol Cell Endocrinol 2012, 351(2):342-350.
• [39]Rendtorff N, Schrijver I, Lodahl M, Rodriguez-Paris J, Johnsen T, Hansen E, et al.: SLC26A4 mutation frequency and spectrum in 109 Danish Pendred syndrome/DFNB4 probands and a report of nine novel mutations. Clin Genet 2013.
• [40]Hall A, Pembrey M, Lutman M, Steer C, Bitner-Glindzicz M: Prevalence and audiological features in carriers of GJB2 mutations, c.35delG and c.101T > C (p.M34T), in a UK population study. BMJ Open 2012, 2:e001238.