Hearing loss is one of the most frequent sensory disorders. It affects approximately one in 700–1000 newborns [1, 2]. It can be the result of genetic mutations or environmental factors, which include ototoxic drugs such as aminoglycoside antibiotics [2]. These types of antibiotics are widely used because of their effectiveness in the treatment of gramnegative infections. They are also easily accessible and inexpensive to produce [3]. Examples of aminoglycosides include streptomycin, neomycin, kanamycin, paromomycin, gentamicin, tobramycin, amikacin, netilmicin, and spectinomycin [4]. They are usually safe to use within recommended limits. However, they are known causes of ototoxicity [4]. For certain genetically susceptible individuals, receiving these medications could result in permanent sensorineural hearing loss. There have been several reports of profound hearing loss in family members receiving aminoglycosides [5-8]. These patients were found to harbor a maternally inherited A1555G mutation located at a highly conserved region of the mitochondrial encoded 12S rRNA gene (
Here, we identified a large Thai family with 11 members reported to have postlingual deafness after receiving aminoglycosides. Mutation analysis showed that all 4 available affected members harbored the A1555G mutation in
We identified a large Thai family with 11 members reported to have postlingual deafness after receiving aminoglycosides. We obtained and examined blood samples from 5 family members; 4 of whom were deaf (
Six milliliters of peripheral blood was obtained from each individual after written informed consent was obtained. Genomic DNA was isolated from white blood cells using a QIAamp DNA blood mini kit according to the manufacturer’s instruction (Qiagen, Valencia, CA, USA). Polymerase chain reaction (PCR)-amplification of the
The presence of the A1555G mutation in other family members was determined by digestion of the PCR products with the restriction enzyme
PCR–Sanger sequencing of III-5 revealed that the patient had a homoplasmic A>G mutation at nucleotide position 1555 of the
In our study, we first analyzed the A1555G mutation in the
With a prevalence of almost 1 in 400 individuals in the British population [9], the A1555G mitochondrial variant could be considered common in some ethnic groups. As long as people with this genetic susceptibility are not given aminoglycosides, they could remain healthy with normal hearing throughout their entire life [9]. Nonetheless, there was an observation that the A1555G mutation could cause hearing loss even without exposure to aminoglycosides. The hearing loss in these cases tends to be later onset and less severe compared with those exposed to aminoglycosides [10]. By contrast, there has been a recent report of a child with a A1555G mutation who has normal hearing despite repeated exposure to aminoglycosides [11]. Factors affecting penetrance of this genetic susceptibility require further investigations.
Aminoglycosides produce their antibacterial effects by binding to the 30S ribosomal subunit of bacterial ribosomes, which alters their conformation. This leads to codon misreading of RNA, induces errors in protein synthesis, and results in bacterial death [12]. Because structural differences lower the drug’s affinity for eukaryotic ribosomes, aminoglycosides do not normally bind to human ribosomes, and therefore are generally safe for human use [4]. However, the mutation at position 1555 from adenine to guanine in human
Our present finding demonstrated that the A1555G mitochondrial mutation causing aminoglycoside-induced deafness, reported in several families worldwide, is also present in the Thai population. This genetic susceptibility is located within human mitochondrial DNA; therefore it is maternally inherited transferring from mothers to their children. Therefore, it is important that medical practitioners in Thailand be aware of this mitochondrial DNA mutation. This mutation should be considered before prescribing aminoglycosides, especially when there is deafness reported in a patient’s family history. Patients who have this mutation should be prescribed with an alternative antibiotic to avoid this preventable deafness.