Genetic and clinical analysis of nonsyndromic hearing impairment in pediatric and adult cases

J Xing; X Liu; Y Tian; J Tan; H Zhao

Open Access

Genetic and clinical analysis of nonsyndromic hearing impairment in pediatric and adult cases

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| Aug 02, 2016

Balkan Journal of Medical Genetics

Volume 19 (2016): Issue 1 (June 2016)

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Published Online: Aug 02, 2016

Page range: 35 - 42

DOI: https://doi.org/10.1515/bjmg-2016-0005

Keywords
Genetic testing, gene, mtDNA A1555G/C1494T, Nonsyndromic hearing impairment (NSHI)

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Mutation rates for patients with NSHI classified by age at first hospital visit.

Mutation rates for patients with NSHI classified by age at onset of deafness.

Frequency of the GJB2 gene variations in patients with NSHI.

Amino Acid	Nucleotide	Number of Alleles	Frequency (%)
E47X	139G>T	1	1.52
R32C	94C>T	1	1.52
G4D	11G>A	1	1.52
W77X	231G>A	1	1.52
59stop	176-191del16	1	1.52
Q80R	239A>G	1	1.52
S139N	416G>A	2	3.03
11stop	30-35delG	3	4.55
299-300delAT	299-300delAT	10	15.15
79stop	235delC	45	68.18
Total		66	100.00

Mutation status in pediatric cases of NSHI cases by pre-lingual or post-lingual onset of deafness.

Mutation Status	Pre-lingual Deafness (≤3 years)	Post-lingual Deafness (>3 and <18 years)	χ² Test	p Value
GJB2:- mutation- no mutation	44 (23.66%)142 (76.34%)	5 (9.80%)46 (90.20%)	4.683	0.031
mtDNA A1555G/C1494T:- mutation- no mutation	18 (9.68%)168 (90.32%)	7 (13.73%)44 (86.27%)	0.695	0.404

Distribution of age of onset in patients with the GJB2 gene and mtDNA mutations.

Mutation Status	Total	Age at Onset			χ² Test	p Value
		≤1 year	>1 and ≤3 years	>3 years
GJB2 gene	49	32 (65.31%)	11 (22.45%)	6 (12.24%)	13.383	0.001
mtDNA mutations	30	8 (26.67%)	9 (30.00%)	13 (43.33%)

Mutation status in pediatric cases of NSHI categorized by age at onset of deafness.

Mutation Status	Infants (n = 186)	Preschool (n = 21)	School Age (n = 30)	χ² Test	p Value
GJB2:- mutation- no mutation	44 (23.66%)142 (76.34%)	2 (9.52%)19 (90.48%)	3 (10.00%)27 (90.00%)	4.685	0.096
mtDNA A1555G/C1494T:- mutation- no mutation	18 (9.68%)168 (90.32%)	2 (9.52%)19 (90.47%)	5 (16.67%)25 (83.33%)	1.363	0.502* Fisher’s exact test

Sequence changes in GJB2 gene mutations in 263 NSHI patients.

Amino Acid	Nucleotide	Number of Affected Alleles		Number of Alleles	Category
		Homozygous	Heterozygous
V27I	79G>A	27	90	144	polymorphism
E114G	341A>G	11	69	91	polymorphism
V37I	109G>A	1	11	13	polymorphism
I203K	608T>C	1	8	10	polymorphism
T123N	368C>A	0	3	3	polymorphism
G4D	11G>A	0	1	1	missense
11stop	30-35delG	1	1	3	deletion/frameshift
R32C	94C>T	0	1	1	missense
E47X	139G>T	0	1	1	missense
59stop	176-191del16	0	1	1	deletion/frameshift
W77X	231G>A	0	1	1	missense
79stop	235delC	15	15	45	deletion/frameshift
Q80R	239A>G	0	1	1	missense
299-300delAT	299-300delAT	3	4	10	deletion/frameshift
S139N	416G>A	1	0	2	missense
T18I	53C>T	0	1	1	novel sequence variation
D50N	148G>A	0	1	1	novel sequence variation
Y38C	203A>G	0	1	1	novel sequence variation
T86R	257C>G	0	1	1	novel sequence variation
G160S	478G>A	0	1	1	novel sequence variation

Comparison of the degree of hearing loss between patients with the GJB2 gene and mtDNA mutations.

Mutation Status	Total	Degree of Hearing Loss				p Value
		Mild	Moderate	Severe	Profound
GJB2 gene	49	3 (6.12%)	5 (10.20%)	9 (18.37%)	32 (65.31%)	<0.001* Fisher’s exact test
mtDNA mutations	30	1 (3.33%)	15 (50.00%)	0 (0.00%)	14 (46.67%)

Mutations status in pediatric cases of NSHI categorized by age at the first hospital visit.

Mutation Status	Infants (n = 72)	Preschool (n = 54)	School Age (n = 70)	χ² Test	p Value
GJB2:- mutation- no mutation	16 (22.22%)56 (77.78%)	14 (25.93%)40 (74.07%)	15 (21.43%)55 (78.57%)	0.384	0.826
mtDNA A1555G/C1494T:- mutation- no mutation	1 (1.39%)71 (98.61%)	2 (3.70%)52 (96.30%)	6 (8.57%)64 (91.43%)	4.314	0.143* Fisher’s exact test

Comparison of the degree of hearing loss by grading standard of 22 patients with mtDNA mutations.

Grading Standard	Degree of Hearing Loss
	Mild	Moderate	Moderate to Severe	Severe	Profound
Guidelines [11]	1	11	‒	3	7
ISO-1964a Compared with 4.0-8.0 kHz p <0.001. b Fisher’s exact test.	5	6	5	1	5
ISO-1997	1	8	‒	5	8
0.25-8.0 kHz	0	6	7	2	7
1.0-4.0 kHz	0	4	5	7	6
4.0-8.0 kHz	0	0	0	7	15

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Genetic and clinical analysis of nonsyndromic hearing impairment in pediatric and adult cases

Article Category: Original Article

Published Online: Aug 02, 2016

Page range: 35 - 42

DOI: https://doi.org/10.1515/bjmg-2016-0005

KeywordsGenetic testing, gene, mtDNA A1555G/C1494T, Nonsyndromic hearing impairment (NSHI)

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Frequency of the GJB2 gene variations in patients with NSHI.

Mutation status in pediatric cases of NSHI cases by pre-lingual or post-lingual onset of deafness.

Distribution of age of onset in patients with the GJB2 gene and mtDNA mutations.

Mutation status in pediatric cases of NSHI categorized by age at onset of deafness.

Sequence changes in GJB2 gene mutations in 263 NSHI patients.

Comparison of the degree of hearing loss between patients with the GJB2 gene and mtDNA mutations.

Mutations status in pediatric cases of NSHI categorized by age at the first hospital visit.

Comparison of the degree of hearing loss by grading standard of 22 patients with mtDNA mutations.

Keywords
Genetic testing, gene, mtDNA A1555G/C1494T, Nonsyndromic hearing impairment (NSHI)