Objectives: The aim of this work was to assess the type and site of the 35delG gene mutation in patients presenting with profound SNHL and scheduled for cochlear implantation. The secondary objectives were to determine their geographical distribution throughout Egypt, screening of the parents for the mutation, and to correlate the type of mutation with clinical severity and outcomes after surgery. Methods: The study was carried out on 100 consecutive patients scheduled for cochlear implantation. Patients with syndromic hearing loss or noncongenital hearing loss (trauma, infections, and ototoxicity) were excluded. All patients were subjected to detailed history taking including geographic tagging for their origins in Egypt, imaging (CT and MRI cochlear implantation protocols), full audiological evaluation (PTA, ABR, and TEOAE), and genetic screening for GJB2 mutation using Invitrogen PCR mix and ApaI restriction enzyme (North America, CA, 10572-014). The parents of mutation-positive patients were also subjected to audiological and genetic analysis. All patients were subjected to postimplantation evaluation of hearing after 6 and 12 months. Results: There were 64 males and 36 females from 98 families. Ages ranged between 1.9 and 7 years (mean 3.72 years). They originated from all over Egypt but the majority came from the Giza and Cairo areas. The 35delG mutations were found in exon 2 in 31% of the cases and all were heterozygous. In the parents, 18 mothers and 13 fathers were positive but only 8 had mild to moderate SNHL. Hearing evaluation by pure tone and speech discrimination scores at 6 and 12 months showed that the 35delG children had a statistically better result compared to the children without this mutation. Conclusion: The prevalence of the 35delG mutation in nonsyndromic children in this sample was 31% which is different from previous studies in the Egyptian population but close to the values found in other populations in the Mediterranean basin.

1.
Bieber FR. Book review: Hereditary Hearing Loss and Its Syndromes (Oxford Monographs on Medical Genetics. No. 28.). Edited by
Gorlin
RJ
,
Toriello
HV
,
Cohen
MM
Jr.
New York, NY
:
Oxford University Press
;
1995
.
457
pp
. ISBN 0-19-506552-2.
Ann Intern Med
.
1995 June
15.
2.
Tekin
M
,
Duman
T
,
Boğoçlu
G
,
Incesulu
A
,
Comak
E
,
Ilhan
I
, et al
Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating
.
Hum Mutat
.
2003
;
21
(
5
):
552
. .
3.
Shearer
AE
,
Smith
RJ
.
Genetics: advances in genetic testing for deafness
.
Curr Opin Pediatr
.
2012
;
24
(
6
):
679
. .
4.
Korver
AM
,
Smith
RJ
,
Van Camp
G
,
Schleiss
MR
,
Bitner-Glindzicz
MA
,
Lustig
LR
, et al
Congenital hearing loss
.
Nat Rev Dis Primers
.
2017
;
3
:
16094
. .
5.
Denoyelle
F
,
Marlin
S
,
Weil
D
,
Moatti
L
,
Chauvin
P
,
Garabédian
EN
, et al
Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling
.
Lancet
.
1999
;
353
(
9161
):
1298
. .
6.
Denoyelle
F
,
Weil
D
,
Maw
MA
,
Wilcox
SA
,
Lench
NJ
,
Allen-Powell
DR
, et al
Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene
.
Hum Mol Genet
.
1997
;
6
(
12
):
2173
.
7.
Sloan-Heggen
CM
,
Bierer
AO
,
Shearer
AE
,
Kolbe
DL
,
Nishimura
CJ
,
Frees
KL
, et al
Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss
.
Hum Genet
.
2016
;
135
(
4
):
441
. .
8.
Del Castillo
FJ
,
Del Castillo
I
.
DFNB1 non-syndromic hearing impairment: diversity of mutations and associated phenotypes
.
Front Mol Neurosci
.
2017
;
10
:
428
.
9.
Kenneson
A
,
Van Naarden Braun
K
,
Boyle
C
.
GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review
.
Genet Med
.
2002
;
4
(
4
):
258
74
.
10.
Manni
F
,
Leonardi
P
,
Barakat
A
,
Rouba
H
,
Heyer
E
,
Klintschar
M
, et al
Y-chromosome analysis in Egypt suggests a genetic regional continuity in Northeastern Africa
.
Hum Biol
.
2002
;
74
(
5
):
645
.
11.
Stevanovitch
A
,
Gilles
A
,
Bouzaid
E
,
Kefi
R
,
Paris
F
,
Gayraud
RP
, et al
Mitochondrial DNA sequence diversity in a sedentary population from Egypt
.
Ann Hum Genet
.
2004
;
68
(
Pt 1
):
23
39
. .
12.
Tawfik
S
,
Hassan
DM
.
Genetics of hearing loss in Egypt
.
Middle East J Med Genet
.
2014
;
3
(
2
):
43
8
.
13.
Duman
D
,
Tekin
M
.
Autosomal recessive nonsyndromic deafness genes: a review
.
Front Biosci
.
2012
;
17
:
2213
.
14.
Matsunaga
T
.
Value of genetic testing in the otological approach for sensorineural hearing loss
.
Keio J Med
.
2009
;
58
(
4
):
216
.
15.
Lesperance
MM
,
Winkler
E
,
Melendez
TL
,
Yashar
BM
.
“My Plate is Full”: reasons for declining a genetic evaluation of hearing loss
.
J Genet Couns
.
2018
;
27
(
3
):
597
607
.
16.
Shearer
AE
,
Shen
J
,
Amr
S
,
Morton
CC
,
Smith
RJ
.
A proposal for comprehensive newborn hearing screening to improve identification of deaf and hard-of-hearing children
.
Genet Med
.
2019
;
21
(
11
):
2614
30
.
17.
Van Camp
G
,
Smith
RJH
.
Hereditary hearing loss homepage
.
Proc Natl Acad Sci U S A
.
2007
.
18.
Esser-Leyding
B
,
Anderson
I
.
EARS® (Evaluation of Auditory Responses to Speech): an internationally validated assessment tool for children provided with cochlear implants
.
ORL J Otorhinolaryngol Relat Spec
.
2012
;
74
(
1
):
42
51
.
19.
Abdel Hamid
A
,
El Shazli
M
,
Eldessouki
T
,
Abdel Ghaffar
H
,
Radwan
A
,
Abdel Monem
A
.
Predictors of language and auditory skills in Egyptian children with a cochlear implant
.
EJO
.
2015
.
20.
Usami
S
,
Wagatsuma
M
,
Fukuoka
H
,
Suzuki
H
,
Tsukada
K
,
Nishio
S
, et al
The responsible genes in Japanese deafness patients and clinical application using Invader assay
.
Acta Otolaryngol
.
2008
;
128
(
4
):
446
. .
21.
Chan
DK
,
Chang
KW
.
GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype
.
Laryngoscope
.
2014
;
124
(
2
):
E34
. .
22.
Murgia
A
,
Orzan
E
,
Polli
R
,
Martella
M
,
Vinanzi
C
,
Leonardi
E
, et al
Cx26 deafness: mutation analysis and clinical variability
.
J Med Genet
.
1999
;
36
(
11
):
829
.
23.
Lerer
I
,
Sagi
M
,
Malamud
E
,
Levi
H
,
Raas-Rothschild
A
,
Abeliovich
D
.
Contribution of connexin 26 mutations to nonsyndromic deafness in Ashkenazi patients and the variable phenotypic effect of the mutation 167delT
.
Am J Med Genet
.
2000
;
95
(
1
):
53
.
24.
Simsek
M
,
Al-Wardy
N
,
Al-Khayat
A
,
Shanmugakonar
M
,
Al-Bulushi
T
,
Al-Khabory
M
, et al
Absence of deafness-associated connexin-26 (GJB2) gene mutations in the Omani population
.
Hum Mutat
.
2001
;
18
(
6
):
545
. .
25.
Moreira
D
,
da Silva
D
,
Lopez
P
,
Mantovani
JC
.
Screening of connexin 26 in nonsyndromic hearing loss
.
Int Arch Otorhinolaryngol
.
2015
;
19
(
1
):
30
3
.
26.
Minarik
G
,
Ferakova
E
,
Ficek
A
,
Polakova
H
,
Kadasi
L
.
GJB2 gene mutations in Slovak hearing-impaired patients of Caucasian origin: spectrum, frequencies and SNP analysis
.
Clini Genet
.
2005
;
68
(
6
):
554
7
.
27.
Abidi
O
,
Boulouiz
R
,
Nahili
H
,
Ridal
M
,
Alami
MN
,
Tlili
A
, et al
GJB2 (connexin 26) gene mutations in Moroccan patients with autosomal recessive non-syndromic hearing loss and carrier frequency of the common GJB2-35delG mutation
.
Int J Pediatr Otorhinolaryngol
.
2007
;
71
(
8
):
1239
. .
28.
Batellino
S
,
Rudolf
G
,
Zargi
M
,
Podgrajsek
KT
,
Peterlin
B
.
Connexin 26 (GJB2) and connexin 30 del(GJB6-D13S1830) mutations in Slovenians with prelingual non-syndromic deafness
.
Int Adv Otol
.
2011
;
7
:
372
8
.
29.
RamShankar
M
,
Girirajan
S
,
Dagan
O
,
Ravi Shankar
HM
,
Jalvi
R
,
Rangasayee
R
, et al
Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India
.
J Med Genet
.
2003
;
40
(
5
):
e68
.
30.
Ito
T
,
Noguchi
Y
,
Yashima
T
,
Ohno
K
,
Kitamura
K
.
Hereditary hearing loss and deafness genes in Japan
.
J Med Dent Sci
.
2010
;
57
(
1
):
1
.
31.
Pampanos
A
,
Economides
J
,
Iliadou
V
,
Neou
P
,
Leotsakos
P
,
Voyiatzis
N
, et al
Prevalence of GJB2 mutations in prelingual deafness in the Greek population
.
Int J Pediatr Otorhinolaryngol
.
2002
;
65
(
2
):
101
.
32.
Lucotte
G
.
High prevalences of carriers of the 35delG mutation of connexin 26 in the Mediterranean area
.
Int J Pediatr Otorhinolaryngol
.
2007
;
71
(
5
):
741
. .
33.
Gasparini
P
,
Rabionet
R
,
Barbujani
G
,
Melçhionda
S
,
Petersen
M
,
Brøndum-Nielsen
K
, et al
High carrier frequency of the 35delG deafness mutation in European populations. Genetic Analysis Consortium of GJB2 35delG
.
Eur J Hum Genet
.
2000
;
8
(
1
):
19
. .
34.
Kivisild
T
,
Reidla
M
,
Metspalu
E
,
Rosa
A
,
Brehm
A
,
Pennarun
E
, et al
Ethiopian mitochondrial DNA heritage: tracking gene flow across and around the gate of tears
.
Am J Hum Genet
.
2004
;
75
(
5
):
752
70
. .
35.
El Barbary
N
,
El Belbesy
M
,
Asal
S
,
Kholeif
S
.
Detection of 35delG, 167delT mutations in the connexin 26 gene among Egyptian patients with nonsyndromic sensorineural hearing loss
.
Egypt J Otolaryngol
.
2015
;
31
:
42
6
.
36.
Shahin
H
,
Walsh
T
,
Sobe
T
,
Lynch
E
,
King
MC
,
Avraham
KB
, et al
Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East
.
Hum Genet
.
2002
;
110
(
3
):
284
. .
37.
Azaiez
H
,
Smith
RJ
.
In reference to temporal bone imaging in GJB2 deafness
.
Laryngoscope
.
2007
;
117
(
6
):
1127
. .
38.
Angeli
SI
.
Phenotype/genotype correlations in a DFNB1 cohort with ethnical diversity
.
Laryngoscope
.
2008
;
118
(
11
):
2014
. .
39.
Jun
AI
,
McGuirt
WT
,
Hinojosa
R
,
Green
GE
,
Fischel-Ghodsian
N
,
Smith
RJ
.
Temporal bone histopathology in connexin 26-related hearing loss
.
Laryngoscope
.
2000
;
110
(
2 Pt 1
):
269
. .
40.
Connell
SS
,
Angeli
SI
,
Suarez
H
,
Hodges
AV
,
Balkany
TJ
,
Liu
XZ
.
Performance after cochlear implantation in DFNB1 patients
.
Otolaryngol Head Neck Surg
.
2007
;
137
(
4
):
596
. .
41.
Kenna
MA
,
Wu
BL
,
Cotanche
DA
,
Korf
BR
,
Rehm
HL
.
Connexin 26 studies in patients with sensorineural hearing loss
.
Arch Otolaryngol Head Neck Surg
.
2001
;
127
(
9
):
1037
.
42.
Brownstein
Z
,
Avraham
KB
.
Deafness genes in Israel: implications for diagnostics in the clinic
.
Pediatr Res
.
2009
;
66
(
2
):
128
. .
43.
Green
GE
,
Scott
DA
,
McDonald
JM
,
Teagle
HF
,
Tomblin
BJ
,
Spencer
LJ
, et al
Performance of cochlear implant recipients with GJB2-related deafness
.
Am J Med Genet
.
2002
;
109
(
3
):
167
. .
44.
Bauer
PW
,
Geers
AE
,
Brenner
C
,
Moog
JS
,
Smith
RJ
.
The effect of GJB2 allele variants on performance after cochlear implantation
.
Laryngoscope
.
2003
;
113
(
12
):
2135
. .
45.
Cullen
RD
,
Buchman
CA
,
Brown
CJ
,
Copeland
BJ
,
Zdanski
C
,
Pillsbury
HC
, et al
Cochlear implantation for children with GJB2-related deafness
.
Laryngoscope
.
2004
;
114
(
8
):
1415
. .
46.
Abdurehim
Y
,
Lehmann
A
,
Zeitouni
AG
.
Predictive value of GJB2 mutation status for hearing outcomes of pediatric cochlear implantation
.
Otolaryngol Head Neck Surg
.
2017
;
157
(
1
):
16
. .
47.
Alves
FRA
,
Ribeiro
FDAQ
.
Diagnosis routine and approach in genetic sensorineural hearing loss
.
Braz J Otorhinolaryngol
.
2007
;
73
(
3
):
412
7
.
48.
Nóra
K
,
Anita
G
,
Magdolna
S
,
Marianna
K
,
Ildikó
B
,
Judit
MM
, et al
Etiological factors of sensorineural hearing loss in children after cochlear implantation
.
Orv Hetil
.
2019
;
160
(
21
):
822
8
.
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