<a name="home"></a>Prevalence of the A1555G (12S rRNA) and tRNA Ser(UCN) mitochondrial mutations in hearing-impaired Brazilian patients

Abstract

Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but the contribution of each mutation has not yet been defined in African-derived or native American genetic backgrounds. A total of 203 unselected hearing-impaired patients were screened for the presence of the mitochondrial mutation A1555G in the 12S rRNA gene and mutations in the tRNA Ser(UCN) gene in order to assess their frequency in the ethnically admixed Brazilian population. We found four individuals with A1555G mutation (2%), which is a frequency similar to those reported for European-derived populations in unselected samples. On the other hand, complete sequencing of the tRNA Ser(UCN) did not reveal reported pathogenic substitutions, namely A7445G, 7472insC, T7510C, or T7511C. Instead, other rare substitutions were found such as T1291C, A7569G, and G7444A. To evaluate the significance of these findings, 110 "European-Brazilians" and 190 "African-Brazilians" unrelated hearing controls were screened. The T1291C, A7569G and G7444A substitutions were each found in about 1% (2/190) of individuals of African ancestry, suggesting that they are probably polymorphic. Our results indicate that screening for the A1555G mutation is recommended among all Brazilian deaf patients, while testing for mutations in the tRNA Ser(UCN) gene should be considered only when other frequent deafness-causing mutations have been excluded or in the presence of a maternal transmission pattern.

Non-syndromic hearing impairment in a multi-ethnic population of Northeastern Brazil

“…The mutation was also reported in Brazilians with profound HI who had been treated with aminoglycosides [7,8]. No subjects in the present study reported prior treatment with aminoglycosides, and contrary to previous Brazilian studies the A1555G mutation was not detected in any cases of HI from Monte Santo.…”

“…Although there was no evidence to suggest maternal inheritance of HI in the families studied, the mitochondrial A1555G mutation in MTRNR1 was specifically investigated because of its prior identification in other Brazilian studies, including individuals with no indication of familial recurrence [7]. The mutation was also reported in Brazilians with profound HI who had been treated with aminoglycosides [7,8].…”

“…Several studies investigating the genetic basis of HI have, however, demonstrated the presence of a range of mostly recessive mutations [7][8][9][10][11].…”

Rastreamento da mutação mitocondrial A1555G em pacientes com deficiência auditiva sensorioneural

“…Only one of these positive cases was associated with an assumed aminoglycoside exposure; no mutation was found in the control group composed by black, white or Asian (Japanese or Chinese) ethnic groups. 30 These results -which are different from our study -may be explained by the highly heterogeneous ethnic composition of the Brazilian population that resulted from racial mixing; this may explain prevalence variations in different Brazilian regions.…”

“…17,30 Understanding the underlying causes of hearing loss caused by aminoglycoside exposure is essential for therapy -especially in neonatal ICUs -and for genetic counseling and early rehabilitation. This is necessary for including or returning these patients to their social and professional activities.…”