© Borgis - New Medicine 3/1999, s. 44-45
Ewa Nowakowska-Szyrwińska1, Łucja Sobieszczańska-Radoszewska1, Teresa Bralczyk1, Wojciech Wiszniewski2, Ewa Obersztyn2, Tadeusz Mazurczak2 Jerzy Bal2
Identification of mutation gene gjb2 in patients with hearing impairment
1 Department of Audiology, National Research Institute of the Mother and Child, Warsaw
Head: Ewa Nowakowska-Szyrwińska, M.D.
2 Department of Medical Genetics, National Research Institute of the Mother and Child, Warsaw
Head: Prof. Tadeusz Mazurczak, M.D.
Summary
Prelingual non-syndromic deafness is the most frequent hereditary sensory defect. In more than 80% of cases, the mode of transmission is autosomal recessive. The molecular investigation was carried out in 48 patients from the audiology department in the National Research Insitute of the Mother and Child. We found mutations of the GJB2 gene in 50% of patients. GJB2 gene accounts for a large percentage of the cases of sensorineural prelingual deafness.
The frequency of inborn and early acquired hearing defects is estimated at 1-2/1000 newborn. It has been assumed that nearly 50% of cases of prelingual deafness are of genetic origin. 80% of them are transmitted in the autosomal recessive mode(1, 2, 3). One of the recently identified genes responsible for autosomal recessive deafness is GJB2, localised on the long arm of chromosome 13 in locus DFNB1. The gene encodes connexin 26 gap junction protein. Mutations found in the gene are responsible for the majority of cases with an autosomal recessive form of deafness (4, 5)
Molecular analysis of patients with deafness has not yet been done in Poland. The aim of this combined work performed by the Departments of Audiology and Genetics was to check the character and frquency of mutations of the GJB2 gene in patients with prelingual deafness.The clinical criteria applied for selection of patients were:
- bilateral profound hearing loss
- deafness as an isolated symptom
The analysis was performed in a group of 48 patients in the Audiological Clinic. The average age of patients was 14.5 and varied from 3 to 19 year. The group consisted of 22 females and 26 males. In every case an informal consent was obtained. A detailed history was taken from all patients and different examinations were performed:
- otolarygeal examinations to search for abnormalities of the nose, pharynx and ears,
- audiological examinations to estimate the form, degree and localisation of hearing deterioration,
- psychological examination to assess intelectual development.
The analysis revealed:
- prelingual and profound bilateral hearing loss (higher than 90 dB) present in 72% - tab. 1,
- familial cases of deafness present in 31.25% of subject, plus sporadic cases in 60.4%,
- otolaryngeal examinations were not informative,
- intelectual development was correct.
Table 1. Assessmant of severity of hearing loss.
| Number tested - 48 | Level of hearing loss (db) |
| > 40 | > 70 | >
90 | Residual |
22 Girls
26 Boys
Mean age 14.5 y. | 4
8,3% | 9
18,75% | 7
14,5% | 28
58,33% |
Group with mutation gjb2
25 children | 1
4,5% | 6
24,5% | 2
8,5% | 16
64,5% |
Group with out mutation gjb2
23 children | 3
13,04% | 3
13,04% | 5
21,74% | 12
52,17% |
GJB2 mutations were found in 25 subjects (tab. 2). In 22 cases the full genotype was established. Amoung mutated alleles one peculiar 35 delG was prevalent and found in 87% of cases. In four alleles other mutations than 35 delG were found: missens mutations M101T, R184p. and one frameshift mutation GGins313. Mutation GGins313 has not been published yet. In a group of 23 patients no mutation was detected. Screening of the GJB2 gene was based on sequencing of the entire coding sequece.The results of audiological,otolaryngeal and psychological examinations obtained for these patients were the same as or similar to the entire group. The subsequent results proved that mutations in the GJB2 gene are responsible to a high degree (50%) for hereditary nonsyndromic deafness in Poland. The calculated frequency is similar to the value obtained for French (55%) and Spanish (40%) populations, but distinc from the frequency found in Germany (16.6%). These differences may arise as a result of different clinical criteria applied to patient evaluation (5, 6).
Table 2. Identification of mutation gjb2 gene.
| Geneotype | Results |
| Allele 1 | Allele 1 | Number of patients | % |
| 35 del G | 35 del G | 18 | 37.6 |
| 35 del G | 313 ins GG | 2 | 4.2 |
| 35 del G | M. 101 T | 1 | 2.0 |
| 35 del G | R 184 P. | 1 | 2.0 |
| 35 del G | ? | 3 | 6.4 |
| ? | ? | 23 | 47.9 |
| | Total | 48 | 100.0 |
Piśmiennictwo
1. Whitek R. et al.: Screening all newborns for hearing loss using trancient evoked otoacoustic emission. Inter. J. of Ped. Otorhinolaryngology.1994, 29:203-217. 2. Vartainen E. et al.: Prevalence and etiology of bilateral sensorineural hearing imoairment in a Finnish childhood population, Int. J. of Ped. Otorhonolaryng. 1997, 41:175-185. 3. Pruszewicz A.: Zarys Audiologii Klinicznej Poznań 1994, Wyd. AM. 4. Kelsell D.P.: Connexin-26 mutations in hereditary non-syndromic sensorineural deafness. Nature 1997, 387; 80. 5. Zelante L.: Connexin-26 associated with the common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum. Mol. Genet. 1997, 9:160. 6.Estivill X. Connexin-26 mutations in sporadic and inherited sensorineural deafness Lancet 1998, 35-394.
