Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Statistical Analysis
2.2. Ethical Approval
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Gene | Exons/Coding Exons, N | Classification of Hearing Loss | Type of Inheritance and Hearing Loss Characteristics | Characteristics of the Tested Patients |
---|---|---|---|---|
SERPINB6 | 8/7 | DFNB91 | AR, congenital or late onset, progressive | 13 pts with a sibling affected with hearing loss, including: 11 pts with early onset prelingual hearing loss and 2 pts with late onset hearing loss in childhood |
TMIE | 4/4 | DFNB6 | AR, congenital severe to profound | 13 pts with a sibling affected with hearing loss, including: 11 pts with early onset prelingual hearing loss and 2 pts with late onset hearing loss in childhood |
COCH | 12/11 | DFNA9 | AD, adult onset, progressive | 13 pts with late onset hearing loss, including: 4 pts with childhood onset and 9 pts with adulthood onset. Pedigrees suggested AD inheritance (n = 3) or sporadic (n = 10) |
ESPN | 13/13 | DFNB36 | AR, congenital severe to profound; AD, late onset progressive | 37 pts with late onset hearing loss, including: 28 pts with childhood onset and 9 pts with adulthood onset. Pedigrees suggested AD inheritance (n = 10) or sporadic (n = 27) |
ACTG1 | 6/5 | DFNA20/26 | AD, late onset, progressive | 37 pts with late onset hearing loss, including: 28 pts with childhood onset and 9 pts with adulthood onset. Pedigrees suggested AD inheritance (n = 10) or sporadic (n = 27) |
KCNQ4 | 14/14 | DFNA2A | AD, late onset, progressive | 37 pts with late onset hearing loss, including: 28 pts with childhood onset and 9 pts with adulthood onset. Pedigrees suggested AD inheritance (n = 10) or sporadic (n = 27) |
GJB3 | 2/1 | DFNA2B | AD, adult onset, progressive; digenic AR (GJB2/GJB3), congenital | 37 pts with late onset hearing loss, including: 28 pts with childhood onset and 9 pts with adulthood onset. Pedigrees suggested AD inheritance (n = 10) or sporadic (n = 27) |
Hearing Loss Groups and Subgroups | N (% of Total) | Pts with Unaffected Parents and a Sibling with Hearing Loss/pt Pedigree Suggestive of AD Inheritance, N (% of Subgroup) | Pts with Biallelic GJB2 Mutations, N (% of Subgroup) | Pts with Monoallelic GJB2 Mutations, N (% of Subgroup) | Pts without GJB2 Mutations, N (% of Subgroup) |
---|---|---|---|---|---|
Onset | |||||
Early prelingual | 104 (52) | 13 (13)/0 (0) | 35 (34) | 4 (4) | 65 (62) |
Early postlingual | 42 (21) | 5 (12)/2 (5) | 6 (14) | 4 (10) | 32 (76) |
Late, in childhood | 44 (22) | 4 (9)/9 (21) | 2 (5) | 4 (9) | 38 (86) |
Late, in adulthood | 10 (5) | 0 (0)/2 (20) | 1 (10) | 0 (0) | 9 (90) |
Total number | 200 (100) | 22 (11)/13 (7) | 44 (22) | 12 (6) | 144 (72) |
Fisher’s exact test | - | 0.831/< 0.0001 | 0.0002 | 0.359 | 0.011 |
Severity | |||||
Mild | 45 (23) | 3 (7)/2 (4) | 3 (7) | 3 (7) | 39 (86) |
Moderate | 33 (17) | 3 (9)/8 (24) | 3 (9) | 5 (15) | 25 (76) |
Severe | 68 (34) | 9 (13)/3 (4) | 23 (34) | 1 (1) | 44 (65) |
Profound | 54 (27) | 7 (13)/0 (0) | 15 (28) | 3 (6) | 36 (66) |
Total number | 200 (100) | 22 (11)/13 (7) | 44 (22) | 12 (6) | 144 (72) |
Fisher’s exact test | - | 0.698/0.0002 | 0.001 | 0.053 | 0.055 |
HGVS, Coding Level | HGVS, Protein Level | N (%) (n = 200) | % Biallelic GJB2 Mutations (n = 44) | Grade and Type of Hearing Loss a |
---|---|---|---|---|
Biallelic | ||||
c.[-23+1G>A];[35delG] | p.[?];[Gly12Valfs*2] | 1 (0.5) | 2.3 | Profound |
c.[-23+1G>A];[101T>C] | p.[?];[Met34Thr] | 1 (0.5) | 2.3 | Mild PostL |
c.[35delG];[35delG] | p.[Gly12Valfs*2];[Gly12Valfs*2] | 28 (14) | 63.6 | 13 profound, 13 severe, 1 moderate, 1 mild |
c.[35delG];[71G>T] | p.[Gly12Valfs*2];[Trp24*] | 1 (0.5) | 2.3 | Profound |
c.[35delG];[101T>C] | p.[Gly12Valfs*2];[Met34Thr] | 1 (0.5) | 2.3 | Moderate PostL |
c.[35delG];[109G>A] | p.[Gly12Valfs*2];[Val37Ile] | 1 (0.5) | 2.3 | Severe |
c.[35delG];[235delC] | p.[Gly12Valfs*2];[Leu79CysfsTer3] | 1 (0.5) | 2.3 | Severe |
c.[35delG];[269T>C] | p.[Gly12Valfs*2];[Leu90Pro] | 1 (0.5) | 2.3 | Moderate PostL |
c.[35delG];[313_326del14] | p.[Gly12Valfs*2];[Lys105Glyfs] | 1 (0.5) | 2.3 | Severe |
c.[35delG];[439G>A] | p.[Gly12Valfs*2];[Glu147Lys] | 1 (0.5) | 2.3 | Severe |
c.[71G>T];[71G>T] | p.[Trp24*];[Trp24*] | 4 (2) | 9.1 | Severe |
c.[101T>C];[101T>C] | p.[Met34Thr];[Met34Thr] | 1 (0.5) | 2.3 | Mild PostL |
c.[250G>A];[416G>A] | p.[Val84Met];[Ser139Asn] | 1 (0.5) | 2.3 | Severe |
c.[313_326del14];[269T>C] | p.[Lys105Glyfs];[Leu90Pro] | 1 (0.5) | 2.3 | Severe PostL |
Total number | 44 (21) |
HGVS, Coding Level | HGVS, Protein Level | N (%) (n = 200) | Grade and Type of Hearing Loss a |
---|---|---|---|
c.[35delG];[=] | p.[Gly12Valfs*2];[=] | 3 (1.5) | 1 profound, 1 severe, 1 moderate |
c.[71G>T];[=] | p.[Trp24*];[=] | 3 (1.5) | 1 severe, 2 moderate |
c.[109G>A];[=] | p.[Val37Ile];[=] | 4 (2) | 2 moderate, 2 mild PostL |
c.[101T>C];[=] | p.[Met34Thr];[=] | 2 (1) | 1 profound, 1 mild PostL |
Total number | 12 (6) |
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Plevova, P.; Tvrda, P.; Paprskarova, M.; Turska, P.; Kantorova, B.; Mrazkova, E.; Zapletalova, J. Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia. Medicina 2018, 54, 28. https://doi.org/10.3390/medicina54020028
Plevova P, Tvrda P, Paprskarova M, Turska P, Kantorova B, Mrazkova E, Zapletalova J. Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia. Medicina. 2018; 54(2):28. https://doi.org/10.3390/medicina54020028
Chicago/Turabian StylePlevova, Pavlina, Petra Tvrda, Martina Paprskarova, Petra Turska, Barbara Kantorova, Eva Mrazkova, and Jana Zapletalova. 2018. "Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia" Medicina 54, no. 2: 28. https://doi.org/10.3390/medicina54020028