University of Oulu

Mitochondrial hearing loss mutations in Northern Finnish preterm and term-born babies

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Author: Soini, Heidi1
Organizations: 1University of Oulu, Faculty of Medicine, Health Sciences
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.1 MB)
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Language: English
Published: Oulu : H. Soini, 2016
Publish Date: 2016-01-22
Thesis type: Master's thesis
Tutor: Uusimaa, Johanna
Rautio, Arja
Hinttala, Reetta
Karjalainen, Minna
Reviewer: Rautio, Arja
Viitala, Pirkko
Introduction: Approximately 3400 babies are born prematurely each year in Finland of which 1–2% will develop a permanent hearing impairment. Premature babies are prone to severe infections and sepsis, therefore antibiotics are often needed during the first few months of their lives. Mitochondrial DNA mutations in the gene coding for mitochondrial ribosomal RNA (MTRNR1), can cause maternally inherited non-syndromic hearing loss. Sometimes the use of a special group of antibiotics, aminoglycosides, can induce the hearing loss in an individual carrying the mutation in MTRNR1. Aminoglycosides are commonly used for treating severe infections in premature infants. Aminoglycosides target the bacterial ribosome and block the protein translation process, so that eventually the bacterial cell dies. It has been speculated that MTRNR1 mutations make the human mitochondrial ribosome more bacterial-like; thus enhancing the affinity of aminoglycosides to clamp on to the human ribosome as well. The sound-sensing cells in the inner ear have a high energy demand and have an abundance of mitochondria. The ribosomal RNA mutation and aminoglycosides together cause apoptosis and permanent damage in these sensitive cells. Materials and methods: In this study, 813 newborns (preterm and term-born babies) were screened for m.1555A>G, m.1095T>C and m.1495C>T mutations in the MTRNR1 gene using PCR, restriction fragment length polymorphism, Sanger sequencing and radioactive S-labeled heteroplasmy quantification techniques. Results and conclusions: The prevalence of m.1555A>G was determined to be 0.12% in the population of Northern Finland. This concurs with the findings from the rest of Europe. As a result, family carrying a heteroplasmic m.1555A>G mutation was identified for the first time from this geographical region. Previously a few large families with m.1555A>G had been identified from Northern Finland. This should be taken into account if non-syndromic hearing loss occurs in a premature baby’s family. In such a case, genetic testing for the m.1555A>G mutation is recommended before administering aminoglycosides. M.1494T>C and m.1095T>C mutations were absent from the study cohort. This result suggests that either the mutations are very rare and the sample size was too small to detect them, or that the mutations do not occur in our population. The results can be directly utilized for safety considerations of aminoglycoside use on preterm babies in Finland. The need for genetic testing of aminoglycoside sensitivity mutations in preterm babies is assessed.
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Copyright information: © Heidi Soini, 2016. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.