Top

BMC Medical Genetics

Published in:

Open Access 01-12-2013 | Research article

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

Authors: Priya Landa, Ann-Marie Differ, Kaukab Rajput, Lucy Jenkins, Maria Bitner-Glindzicz

Published in: BMC Medical Genetics | Issue 1/2013

Abstract

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.

Available only for authorised users

Fraser GR: Association of congenital deafness with goitre (Pendred’s syndrome). Ann Hum Genet. 1965, 28: 201-248.CrossRefPubMed

Kopp P, Pesce L, Solis-S JC: Pendred syndrome and iodide transport in the thyroid. Trends Endocrinol Metab. 2008, 19 (7): 260-268. 10.1016/j.tem.2008.07.001.CrossRefPubMed

Pendred V: Deaf-mutism and goitre. 1896, 2: 532-

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. 10.1093/hmg/7.7.1105.CrossRefPubMed

Bizhanova A, Kopp P: Genetics and phenomics of Pendred syndrome. Mol Cell Endocrinol. 2010, 322 (1–2): 83-90.CrossRefPubMed

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. 10.1016/S0009-9260(98)80125-6.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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. 10.1136/jmg.2004.024208.CrossRefPubMedPubMedCentral

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.PubMed

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. 10.1038/7783.CrossRefPubMed

12.

TROTTER WR: The association of deafness with thyroid dysfunction. Br Med Bull. 1960, 16: 92-98.PubMed

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. 10.1002/humu.1116.CrossRefPubMed

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. 10.1038/ng1297-411.CrossRefPubMed

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. 10.1006/geno.1996.4541.CrossRefPubMed

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. 10.1152/physiolgenomics.00047.2009.CrossRefPubMed

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. 10.1038/ng0398-215.CrossRefPubMed

18.

Glaser B: Pendred syndrome. Pediatr Endocrinol Rev. 2003, 1 (Suppl 2): 199-204.PubMed

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. 10.1086/518314.CrossRefPubMedPubMedCentral

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. 10.1007/s00439-007-0415-2.CrossRefPubMed

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. 10.1016/j.ajhg.2009.04.014.CrossRefPubMedPubMedCentral

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. 10.1016/j.molbrainres.2005.05.003.CrossRefPubMed

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.PubMed

24.

Reimann F, Ashcroft FM: Inwardly rectifying potassium channels. Curr Opin Cell Biol. 1999, 11 (4): 503-508. 10.1016/S0955-0674(99)80073-8.CrossRefPubMed

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. 10.1152/ajprenal.00487.2006.CrossRefPubMedPubMedCentral

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: 30-10.1186/1741-7015-2-30.CrossRefPubMedPubMedCentral

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. 10.1007/s00335-003-2270-3.CrossRefPubMed

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. 10.1056/NEJMoa0810276.CrossRefPubMedPubMedCentral

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. 10.1242/dev.00376.CrossRefPubMed

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): e4471-10.1371/journal.pone.0004471.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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. 10.1016/j.nbd.2011.03.016.CrossRefPubMed

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. 10.1177/0194599812439670.CrossRefPubMed

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. 10.1089/gtmb.2010.0177.CrossRefPubMed

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. 10.1016/j.ijporl.2010.06.002.CrossRefPubMed

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. 10.1159/000231567.CrossRefPubMed

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. 10.1016/j.mce.2012.01.013.CrossRefPubMed

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, 10.1111/cge.12074.

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: e001238-10.1136/bmjopen-2012-001238.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/14/85/prepub

Title: Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4 mutations in pendred syndrome/enlarged vestibular aqueducts
Authors: Priya Landa
Ann-Marie Differ
Kaukab Rajput
Lucy Jenkins
Maria Bitner-Glindzicz
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2013
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-14-85

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2013

The associations between the polymorphisms in the CTLA-4gene and the risk of Graves’ disease in the Chinese population

A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease

Association between a frequent variant of the FTO gene and anthropometric phenotypes in Brazilian children

Studies of association of AGPAT6variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes

Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case–control multicentre study

Development and validation of a multiplex-PCR assay for X-linked intellectual disability