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Otolaryngol Head Neck Surg. Author manuscript; available in PMC 2012 March 21.
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Published in final edited form as:

Otolaryngol Head Neck Surg. 2009 October ; 141(4): 502508. doi:10.1016/j.otohns.2009.07.004.
Mutation analysis of SLC26A4 in patients with enlarged

vestibular aqueduct in mainland China
Samuel Reyes, MD1,*, Guojian Wang, MD2,*, Xiaomei Ouyang, MD1,*, Bing Han, MD2, Li Lin
Du, BS1, Hui Jun Yuan, MD, PhD2, Denise Yan, PhD1, Pu Dai, MD, PhD2, and Xue-Zhong
Liu, MD, PhD1
1Department of Otolaryngology, University of Miami, Miami, FL
2Institute
Of Otolaryngology, General Hospital of Chinese PLA, Beijing 100853, China
Abstract
OBJECTIVEWe have characterized the spectrum of SLC26A4 mutations and clinical features
in a mainland Chinese population with sensorineural non syndromic hearing loss (SNHL) and
enlarged vestibular aqueduct (EVA).
STUDY DESIGNCross-sectional clinical genetic study.
SETTINGTertiary care outpatient otolaryngology clinic.
METHODS32 subjects identified with bilateral EVA using high resolution computed
tomography (CT) were screened for mutations in SLC26A4 by denaturing high-performance liquid
chromatography (DPHLC) and direct sequencing methods.
RESULTSA total of thirteen different mutations were identified in the SLC26A4 gene, five of
which are novel. A total of 88% of the patients harbored biallelic mutations, eleven patients were
homozygotes, and seventeen were compound heterozygotes. Four patients were found to carry a
single SLC26A4 mutation. The IVS7-2A>G mutation was the most frequent, accounting for 60%
of the mutant alleles. We have not found any correlations between the type of SLC26A4 mutations
and the type, degree and progression of hearing loss. There are significant proportions of patients
with asymmetric (26%), progressive (32%), or fluctuating hearing loss (21%).
CONCLUSIONOur data confirm the high prevalence of SLC26A4 mutations in Chinese

patients with sensorineural hearing loss (SNHL) and EVA. We could not establish any
relationship between genotype and phenotype. However, high incidence of asymmetric,
progressive, and fluctuating hearing loss found in the current study indicates that patients with
those features should be routinely screened for SLC26A4 mutation in addition to diagnosis of EVA
using CT or magnetic resonance imaging.
2009 American Academy of Otolaryngology Head and Neck Surgery Foundation, Inc. Published by Mosby, Inc. All rights
reserved.
Corresponding author: Dr. Xue Zhong Liu Department of Otolaryngology (D-48) University of Miami 1666 NW 12th Avenue,
Miami, FL 33136, USA [email protected] Tel.: 305-243-5695; fax: 305-243-4925 .
*These authors contributed equally to this work
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
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Poster presentation at the American Academy of OtolaryngologyHead and Neck Surgery (AAO-HNS HNS) annual meeting,
Washington, DC, September 16, 2007.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Reyes et al.
Page 2
INTRODUCTION
SLC26A4 is the gene responsible for both Pendred syndrome (SNHL, enlarged vestibular
aqueduct-EVA and goiter) and non-syndromic recessive deafness DFNB4. Located on the
long arm of chromosome 7, the SLC26A4 gene is made up of twenty-one exons. The
encoded protein, pendrin, is expressed in nonsensory cells in the cochlear scala media,
thyroid, renal, uterine and placental tissue. Pendrin is thought to be involved in anion
transport, although its remains unclear how this leads to cochlear dysfunction. Enlargement
of the vestibular aqueduct is the most common anomaly associated with mutations of
SLC26A4 and is genetically characterized as a non-syndromic autosomal recessive disorder
(DFNB4, OMIM 600791). The molecular genetic basis for the hearing loss associated with
EVA was investigated in different ethnic populations. It is clear that EVA is associated with
the mutations of the SLC26A4 (PDS) gene in many racial populations. More than 150
SLC26A4 mutations have been described in different populations.
In the present study, we screened DNA for SLC26A4 mutations in a Chinese cohort of deaf
probands with SNHL and EVA. Using the audiological classification criteria of genetic
deafness proposed by the European Workshop on Genetic Hearing Loss,1 we analyzed
audiological data to characterize the clinical features and spectrum of SLC26A4 mutations in
the mainland Chinese patients.
MATERIALS AND METHODS

Subjects and Audiology
From a Chinese cohort of patients with suspected genetic hearing loss, we identified 32
subjects (3 from multiplex and 29 from simplex families) with EVA using high-resolution
computed tomography (HRCT) in the Department of Otolaryngology, Head and Neck
Surgery, Chinese Peoples Liberation Army General Hospital (Beijing, China). The project
was approved by the Ethic Committee of Chinese PLA General Hospital. Written informed
consent was obtained from all of the participants prior to donation of a blood sample.
Criteria for the diagnosis of EVA was a vestibular aqueduct diameter of >1.5 mm measured
midway between operculum and the common crus.2 All subjects were examined
otoscopically, and pure tone audiometry was performed as well as immittance testing
(tympanometry and acoustic reflexes) for assessment of the integrity and function of the
middle ear. Air conduction thresholds were measured at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4
kHz, 6 kHz and 8 kHz and bone conduction thresholds at 0.5, 1, 2, 4 and 6 kHz. When
output of the bone conduction audiometer is beyond vibration perception threshold in pure
tone test, we are not able to determine whether what patients perceive is sound or vibration;
for example, the vibration perception threshold on mastoid process at 250Hz is about 40dB
HL. Therefore, we end the test when the output of the bone conduction reaches 40dB, 50dB,
60dB, 60dB and 60dB HL in 250, 500, 1000, 2000, 4000 Hz respectively. For this reason,
the maximum output of the machine is always designed to be limited within 70dB and the
air bone gaps (ABG) were not obtained for 1000Hz, 2000Hz and 4000Hz. The results of the
pure tone audiograms were analysed using the audiological classification criteria of genetic
deafness proposed by the European Workshop on Genetic Hearing Loss. The severity of
hearing impairment was applied to the better hearing ear, averaged over 0.5, 1, 2, and 4 kHz
and was categorized as follows: Mild, >20 dB and <=40 dB; Moderate, >40 dB and <70 dB;
Severe, >70 dB and <95 dB; Profound >95 dB. Asymmetry is defined by >10 dB difference
between the ears in at least at two frequencies with a difference in the pure tone average
between the ears of >20 dB; Progression A deterioration of >15 dB in the pure tone
average within a 10 year period. A comprehensive history inquiry and physical examinations
were performed on all the subjects in order to exclude cases of the syndromic deafness or
induced from environmental causes (e.g. aminoglycoside-induced or infections).
Reyes et al.
Page 3
Mutation analysis
Genomic DNA sample of each subject was extracted from whole blood using a DNA Blood
Kit (Watson Biotechnologies Inc, Shanghai, China). All 21 exons and the intron-exon
boundaries of the SLC26A4 gene were sequenced in each of the subjects with an EVA. In
addition, a total of 200 matched controls of Chinese background with normal hearing were
screened for SLC26A4 mutation by high-performance liquid chromatography (DPHLC)
followed by direct sequencing of amplicons with abnormal elution profiles. In brief, DNA
sample were first amplified by polymerase chain reaction (PCR) using primers flanking each
exon. PCR was conducted in a volume of 20l which contained 40 ng of genomic DNA, 400
M dNTP, 1.25 units of proTaq DNA polymerase, 0.2M intragenic primers and 2.5mM
MgCl2. Sequencing was performed on an Applied Biosystems 3100-Avant Genetic
Analyzer. Sequence data were compared with the published sequence of SLC26A4 gene
(ENSG00000091137) using GeneTool Lite 1.0 software program.
RESULTS
A total of 32 SNHL patients with EVA including 19 males and 13 females were investigated
(Table 1). Figure 1 shows a pedigree of a simplex case and the CT scan from a proband
patient. All subjects had bilateral SNHL. One patients audiometric data was not available
among the patients (Table 1). Audiogram of ten patients (20 ears) shows a characteristic of
conductive or mixed hearing loss in low frequencies (250Hz and 500Hz) and sensorineural
hearing loss in middle and high frequencies. The air bone gaps (ABG) of 20 ears ranges
from 15dB~90dB at 250Hz and from 20dB~60dB at 500Hz (Table 2). No mild hearing loss
was found in the present study. A total of 48% (15/31) of patients with SLC26A4 mutations
had profound loss, 36% (11/31) had severe loss, and 16% (5/31) had moderate loss. Some
patients with profound hearing loss may still have some measurable residual hearing,
especially in low frequency. We consider the hearing loss progressive when the residual
hearing continues to deteriorate in one or both ears. The symmetry of hearing loss detected
in the 23 (74%) probands, is reported in Table 1. Twenty-two (69%) patients had a
prelingual ( 2 year old) onset of hearing loss with a mean age-of-onset of 1.02 years. Ten
subjects were found having progressive hearing los. Average follow-up time was 9.5 years,
with a range from 1 to 19 years. Six of the patients had fluctuating hearing loss.
A total of thirteen different mutations were identified (Tables 3). The mutations were
biallelic in 28 of the 32 subjects (88%). Of these, 11 subjects have homozygotic mutations,
17 were compound heterozygotes. One case had complex allele with three variants. In four
probands, only one SLC26A4 mutation was detected. Clinical characteristics are provided in
Table 1. The most common mutation was a splice site mutation in intron 7 (IVS7-2A>G)
found in 26 of 32 patients which accounts for 60% (36 /60) mutant alleles. The IVS7-2A>G
was detected in 10 homozygotes and 15 compound heterozygotes. Two cases were
heterozygous with the second allele remaining unidentified. The ten homozygous patients
with IVS7-2A>G had severe to profound deafness. Of the six patients with fluctuating
hearing loss, five carried IVS7-2A>G mutation in a compound heterozygous state and one
was homozygous for IVS7-2A>G. There was no clear relationship between genotype and
phenotype identified.
The second most frequent mutation was p.H723R accounting for 15 % (9/60) mutant alleles.
Overall, seven missense mutations, two splice site mutations, and four frameshift mutations
were identified. Of these mutations, a total of 5 variants had not been previously reported,
including two missense mutations (p.H135R and p.V545A) and three frameshift mutations
(c.1555-1556delAA, c.1687-1692delA and c.2082delA). None of these variants was
detected in any of the 200 normal hearing subjects of Chinese background. A schematic
Reyes et al.
Page 4
distribution of the mutations identified in the present study and reported mutations among
Chinese along the SLC26A4 gene is shown in Figure 2.
Three different previously unreported mutations causing frameshifts with premature

termination were detected in this study. The first new deletion is a two-base deletion of AA
at nucleotide position 1555-1556 in exon 14. This mutation leads to a frameshift at codon
519, with a stop codon occurring at codon 539 or 20 amino acids residues downstream.This
framshift mutation was detected in a complex allele state with three variants (c.1548insC /c.
1555-6delAA/p.H723R) in a proband. The second novel frameshift mutation consists of a
deletion of A at nucleotide position 1687-92 in exon 15, which results in a frameshift,
starting at codon 563, with a subsequent premature stop codon at the 572th amino acid
residue. The mutation was identified in a compound heterozygous state with a splice site
mutation IVS7-2A>G. Finally, the c.2082delA was also found in a compound heterozygous
state with IVS7-2A>G mutation. This mutation caused a frameshift at condon 694 resulting
in a premature stop at codon 699 in exon 18.
In the present study, five missense mutations and one frameshift mutation, including c.
1173C>A/p.S391R, c.1174A>T/p.N392Y, c.1226G>A/p.R409H, c.1229C>T/p.T410M, c.
2168A>G/p.H723R and c.1548insC have been previously described.3-6 Two novel missense
mutations were identified in the present study. The c.404A>G/p.H135R mutation was
detected in a compound heterozygous state with the c.2168A>G/p.H723R. The p.H135R
change due to a A>G transition at nucleotide position 404 in exon 4 results in a replacement
of histidine, that has a positively charged imidazole functional group with arginine, an
amino acid with a positively charged guanidino group. This change occurs within the first
extracellular domain of the SLC26A4 protein. Another new mutation c.1634T>A/p.V545A
was identified in a compound heterozygous state with IVS7-2A>G. The two missense
changes might be pathogenic on the basis of the following criteria: 1) these substitutions
were absent in 200 unrelated control DNA samples of Chinese background; 2) the two
newly identified missense changes are located within functional domains of the SLC26A4
protein; 3) sequence comparison across species demonstrates conservation of the p.H135
and p.V545 residues in human, rat, mouse and xenopus (Fig 3).
DISCUSSION
Mutations in SLC26A4 are the major genetic cause of Pendred Syndrome (PS) and DFNB4
in many racial populations. To date, more than 100 mutations causing Pendred syndrome
and nonsyndromic (EVA) sensorineural hearing loss have been reported in the PDS gene
(http://www.healthcare.uiowa.edu/labs/pendredandbor//slcMutations.htm). Moreover, a
significant difference in the frequency and distribution of the mutations has been observed in
different populations. Among Asian populations, a distinct spectrum of SLC26A4 mutations
in patients associated with EVA with highly prevalent founder mutations has been observed,
such as p.H723R in Japan and Korea and IVS7-2A>G in China.3,6-9 Park et al performed a
mutation screening of the seven exons of the SLC26A4 gene in 274 East Asians and 318
South Asians deaf probands with sporadic or familial severe to profound prelingual
deafness, including 86 Chinese affected subjects. They demonstrated mutations in SLC26A4
in about 5.5% in both groups and identified 3 mutations (p.S252P, IVS7-2 A>G, p.N392Y)
in 5 out of 86 (5.8%) Chinese probands.6 Tsukamoto et al reported that causative mutations
have been identified in 90% of typical Pendred families, and in 78% of families with
sensorineural hearing loss associated with EVA in Japan. Of the mutations detected, 53%
were the p.H723R mutation.3 Campbell et al stated that p.L236P (16%), p.T416P and
IVS8+1G>A were the three frequent mutations in the Caucasian population 10. In the
Spanish population the most frequent mutation is p.Q514K (17%).11
Reyes et al.
Page 5

To date, more than 40 mutations have been reported among Chinese (Fig 2). IVS7-2A>G
mutation was the most common mutation accounting for 22 -58% of all the mutant alleles in
Chinese patients with hearing loss associated with EVA or both EVA and Mondini dysplasia
(MD).7-9 Wang et al7 reported that biallelic mutations were identified in 88% of patients
from the simplex families. Overall, up to 98% patients were found to have at least one
possible pathogenic variant in SLC26A4. The IVS7-2A>G mutation accounted for 58 %
(102/177) of all the mutant alleles. The IVS7-2A>G mutation caused skipping of exon 8
with a resulting stop codon at position 311, leading to a predicted truncated protein. The
mutation was first reported in a Turkish family12 and subsequently detected in deaf subjects
from Japan, Korea, and China. IVS7-2A>G has not been found in western populations,
including deaf patients in the United States
(http://www.healthcare.uiowa.edu/labs/pendredandbor//slcMutations.htm). Dai et al8 have
recently reported a comprehensive study of the prevalence of IVS7-2A>G mutation in an
analysis of 3271 deaf subjects from 27 regions of 24 provinces of China. The detection rate
was found to range from 28% to below 1% based on ethnicity. The results showed that
genetic test for the IVS7-2A>G mutation alone would identify the molecular cause in up to
812% of deaf patients in a few eastern and central regions of China. However, the
IVS7-2A>G mutation occurs at a much lower frequency (0.000-0.019) among ethnic groups
in the southwest and northwest regions of China. The data suggest that for subjects that are
negative for the IVS7-2A>G mutation, further mutational analysis of the full SLC26A4 gene
or other deafness-related genes will be necessary.
In the present study, the prevalence of SLC26A4 mutation was 100% (32/32) in this cohort
of Chinese patients with bilateral EVA. Biallelic mutations were detected in 88% (28/32) of
patients, eleven of whom were homozygous. Four subjects were found to carry a single
SLC26A4 mutation. We identified SLC26A4 mutations in 60 of the 64 alleles tested (94%)
(Table 3). The IVS7-2A>G mutation was the most common form accountting for 60%
(36/60) of all the mutant alleles, which supports the view that the IVS7-2A>G mutation is
indeed the most common mutation found in genetic deafness patients with EVA of Chinese
background. Thus, if screening for mutations in SLC26A4 is considered, it is reasonable to
screen for the IVS7-2A>G mutation first. A total of 5 new mutations were identified in this
study including two missense mutations and three frameshift mutations. The distribution of
the five novel mutations described in the present study along the SLC26A4 gene is shown in
Figure 1: the c.404A>G/p.H135R mutation occurs in the first extracellular region; two of the
mutations (c.1555-6delAA; c.1634T>A/p.V545A) are located in the cytoplasmic domain;
the c.1687-92delA is detected in the transmembrane domain; and the c. 2082delA mutation
was found within the STAS domain (sulfate transporter and antisigma antagonist) at the Cterminal region of the protein, which seems to be involved in the binding of nucleotides and/
or the interaction with the cAMP-dependent chloride channel CFTR (cystic fibrosis
transmembrane conductance regulator.13 STAS domain is proposed to be important for
proper localization to the plasma membrane14 and regulation of anion transport activity.13,15
The identification of the role of SLC26A4 in non-syndromic deafness with EVA may allow
us to investigate any possible genotype-phenotype relation by combining molecular genetic
study and an audiological analysis. In the present study, the following features of the
SLC26A4-related deafness were observed. The hearing impairment in 69% of the patients
has a prelingual onset. The degree of hearing loss varies greatly ranging from moderate to
profound, but a higher prevalence of severe and profound hearing loss was found. We have
not found any correlations between the type of SLC26A4 mutations and the audiogram.
There are significant proportions of patients with asymmetric (26%), progressive (32%), or
fluctuating hearing loss (21%). These audiological features are not common in other
recessive forms of non-syndromic hearing loss. Clearly more cases and comprehensive
audiological studies are needed to address any potential genotype and phenotype correlation.
Reyes et al.
Page 6
CONCLUSION
Our data confirm the high prevalence of SLC26A4-related deafness in Chinese SNHL and
EVA patients and support the view that a unique spectrum of the PDS gene in Chinese,
which is distinct from that found in the other ethic populations. All categories of hearing
loss severity except for mild loss were found. The SLC26A4- related deafness appears to be
prevalent in severe to profound loss. Although no clear genotype and phenotype correlation
was found, high incidence of asymmetric, progressive, and fluctuating hearing loss detected
in the current study warrants further investigations to define any molecular basis/
environmental factor of these uncommon features in non-syndromic forms of recessive
deafness. The high detection rate of SLC26A4 mutations in Chinese with SNHL and EVA
indicates that screening SLC26A4 mutations should be offered to Chinese deaf patients with
EVA.
Acknowledgments
The work is supported by NIH DC 05575 and by the National Natural Science Foundation of China 30528025. We
thank the families for their kind participation in this study.
REFERENCES
1. European Concerted Action Project on Genetics of Hearing Impairment. Study group on

terminology, definition and hearing assessment. Nov. 1996 Newsletter No
2http://hear.unife.it/he_infol.htm
2. Lasak JM, Welling DB. The enlarged vestibular aqueduct syndrome. Curr Opin Otolaryngol Head
Neck Surg. 2000; 8:3803.
3. Tsukamoto K, Suzuki H, Harada D, et al. Distribution and frequencies of PDS (SLC26A4) mutations
in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct:
a unique spectrum of mutations in Japanese. Eur J Hum Genet. 2003; 11:91622. [PubMed:
14508505]
4. Coyle B, Reardon W, Herbrick JA, et al. Molecular analysis of the PDS gene in Pendred syndrome
(sensorineural hearing loss and goitre). Hum Mol Genet. 1998; 7:110512. [PubMed: 9618167]
5. Van Hauwe P, Everett LA, Coucke P, et al. Two frequent missense mutations in Pendred syndrome.
Hum Mol Genet. 1998; 7:1099104. [PubMed: 9618166]
6. Park HJ, Shaukat S, Liu XZ, et al. Origins and frequencies of SLC26A4 (PDS) mutations in east and
south Asians: global implications for the epidemiology of deafness. J Med Genet. 2003; 40:2428.
[PubMed: 12676893]
7. Wang QJ, Zhao YL, Rao SQ, et al. A distinct spectrum of SLC26A4 mutations in patients with
enlarged vestibular aqueduct in China. Clin Genet. 2007; 72:24554. [PubMed: 17718863]
8. Dai P, Li Q, Huang D, et al. SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause
of hearing loss. Genet Med. 2008; 10:58692. [PubMed: 18641518]
9. Hu H, Wu L, Feng Y, et al. Molecular analysis of hearing loss associated with enlarged vestibular
aqueduct in the mainland Chinese: a unique SLC26A4 mutation spectrum. J Hum Genet. 2007;
52:4927. [PubMed: 17443271]
10. Campbell C, Cucci RA, Prasad S, et al. Pendred syndrome, DFNB4, and PDS/SLC26A4
identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat.
2001; 17:40311. [PubMed: 11317356]
11. Pera A, Villamar M, Viuela A, et al. A mutational analysis of the SLC26A4 gene in Spanish
hearing-impaired families provides new insights into the genetic causes of Pendred syndrome and
DFNB4 hearing loss. Eur J Hum Genet. 2008:19.
12. Coucke PJ, Van Hauwe P, Everett LA, et al. Identification of two different mutations in the PDS
gene in an inbred family with Pendred syndrome. J Med Genet. 1999; 36:4757. [PubMed:
10874637]
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13. Ko SB, Zeng W, Dorwart MR, et al. Gating of CFTR by the STAS domain of SLC26 transporters.
Nat Cell Biol. 2004; 6:34350. [PubMed: 15048129]
14. Chernova MN, Jiang L, Shmukler BE, et al. Acute regulation of the SLC26A3 congenital chloride
diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes. J Physiol. 2003; 549:319.
[PubMed: 12651923]
15. Zalzal GH, Tomaski SM, Vezina LG, et al. Enlarged vestibular aqueduct and sensorineural hearing
loss in childhood. Arch Otolaryngol Head Neck Surg. 1995; 121:238. [PubMed: 7803018]

Reyes et al.
Page 8
Figure 1.
A. The pedigree of one EVA subject with simplex family history. B. Appearance of
temporal bone with EVAS in CT image. The arrow indicates the enlarged vestibular
aqueduct (right).

Reyes et al.
Page 9

Figure 2.
A schematic representation of the relative linear location of mutations of SLC26A4 gene

identified in present study and all SLC26A4 mutations among Chinese (refs 11, 14, 15).
Novel mutations from this study were in bold italic.

Reyes et al.
Page 10

Figure 3.
Multiple sequence alignment showing conservation of residues H135 and V545.

20
11
23
12
13
14
0.5
13
13
33
19
20
21
22
23
24
25
4.5
11
18
12
10
4.5
17
7.5
12
1.6
3.5
10
16
1.4
15
13
3.6
3.1
Age
(Years)
Subjects
number
F
Sex
birth
birth
2Y
10Y
3Y
3M
2Y
11M
1Y
2Y
10M
4Y
4Y
2Y
4Y
11M
2Y
4Y
4M
4Y
1Y3M
3Y6M
1Y6M
birth
4Y
Onset
Profound/ Profound
Profound/ Profound
moderate/
profound
profound/
moderate
severe/moderate
Profound/ Profound
profound/severe
severe/moderate
Profound/ Profound
Severe/severe
Profound/ Profound
Profound/ Profound
Severe/severe
Severe/severe
moderate/severe
Profound/ Profound
severe/profound
Profound/ Profound
Severe/severe
NA
Severe/severe
Severe/severe
Profound/ Profound
severe/profound
Profound/ Profound
Severity(L/R)
No change
No change
No change
progressive
No change
No change
fluctuating
No change
progressive
fluctuating
progressive
progressive
progressive
fluctuating
fluctuating
progressive
No change
No change
progressive
NA
No change
No change
NA
NA
fluctuating
Evolution
simplex
simplex
simplex
simplex
simplex
multiplex
simplex
simplex
simplex
simplex
simplex
multiplex
simplex
simplex
simplex
simplex
simplex
simplex
simplex
simplex
simplex
simplex
simplex
simplex
simplex
Family
history
Characteristics of 32 patients screened for SLC26A4 mutations.
EVA(3.5)
EVA(4)
EVA(5)
EVA(4)
EVA(3)
EVA&CD
(3.5)
EVA(4)
EVA(2.5)
EVA(4)
EVA(3)
EVA(4)
NA(3.5)
EVA(3.5)
EVA(2.5)
EVA(3)
EVA(3.5)
EVA(3.5)
EVA(4)
EVA(3)
EVA(3.5)
EVA(3)
EVA(4)
EVA(3.5)
EVA(2.5)
EVA(3)
CT scan
(mm)
Table 1
Reyes et al.
Page 11
12
9
4.5
21
10
2.5
27
28
29
30
31
32
Sex
birth
4Y
2Y
3Y
2Y
2M
2M
Onset
Profound/ Profound
Severe/severe
Severe/severe
Profound/ Profound
Profound/ Profound
Profound/ Profound
Profound/ Profound
Severity(L/R)
No change
progressive
fluctuating
NA
progressive
No change
No change
Evolution
multiplex
simplex
simplex
simplex
simplex
simplex
simplex
Family
history
EVA(3)
EVA(4.5)
EVA(3.5)
EVA(3)
EVA(3.5)
EVA(4)
EVA(2.5)
CT scan
(mm)
CD, bilateral cochlear dysplasia; EVA, bilateral enlarged vestibular aqueduct; NA, not available
0.2
26

Age
(Years)
Subjects
number
Reyes et al.
Page 12

60
65
50
50
60
70
100
70
70
80
55
40
50
50
50
55
65
45
25
60
A-B
gap
20
25
25
40
40
55
50
40
65
50
BC
50
70
70
70
70
85
90
70
105
80
AC
30
45
45
30
30
30
40
30
40
30
A-B
gap
500Hz (left)
20
10
10
15
35
25
40
20
BC
60
35
75
55
55
60
100
80
65
80
AC
55
15
75
45
45
45
65
55
25
60
A-B
gap
250Hz (right)
BC = bone conduction; AC = air conduction; A-B gap = air bone gap.
28
10
18
31
15
16
35
15
25
25
13
30
45
10
29
20
AC
250Hz (left)
BC
Subjects
number
10
20
25
40
40
40
50
40
60
50
BC
40
50
85
60
60
85
100
80
85
80
AC
30
30
60
20
20
45
50
40
25
30
A-B gap
500Hz (right)
Bone conduction and air conduction thresholds at 250Hz and 500Hz for the right and left ears*
Table 2
Reyes et al.
Page 13
Reyes et al.
Page 14
Table 3
Details of genotypes of SLC26A4 detected in 32 SNHL associated with EVA patients in a Chinese population
Genotypes
Number of individuals
IVS7-2A>G/IVS7-2A>G
10
IVS7-2A>G/p.S391R
IVS7-2A>G/p.N392Y
IVS7-2A>G/p.R409H
IVS7-2A>G/p.V545Aa
IVS7-2A>G/c.1687-92delAa
IVS7-2A>G/IVS15+5G>A
IVS7-2A>G/p.H723R
IVS7-2A>G/c.2082delAa
IVS7-2A>G/WT
p.H135Ra/ p.H723R
p.N392Y/p.T410M
c.1548insC /c.1555-6delAAa/p.H723R
IVS15+5G>A/WT
p.H723R/p.H723R
Novel changes identified in the present study


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Mutation analysis of SLC26A4 in patients with enlarged

Of Otolaryngology, General Hospital of Chinese PLA, Beijing 100853, China

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CONCLUSIONOur data confirm the high prevalence of SLC26A4 mutations in Chinese

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MATERIALS AND METHODS

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Three different previously unreported mutations causing frameshifts with premature

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1. European Concerted Action Project on Genetics of Hearing Impairment. Study group on

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A schematic representation of the relative linear location of mutations of SLC26A4 gene

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Multiple sequence alignment showing conservation of residues H135 and V545.

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Characteristics of 32 patients screened for SLC26A4 mutations.

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BC = bone conduction; AC = air conduction; A-B gap = air bone gap.

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Novel changes identified in the present study

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