Evaluation of mitochondrial tRNASer(UCN) G7444A mutation associated with non-syndromic hearing loss in eleven Han Chinese pedigrees
1.Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, 325035; 2.Renji College, Wenzhou Medical University, Wenzhou, 325035; 3.Institute of Genetics, Zhejiang University, Hangzhou, 310058
Abstract：Objective: To report the clinical, genetic and molecular characteristics of 11 Han Chinese pedigrees with mitochondrial tRNASer(UCN) G7444A mutation and explore the role of mitochondrial tRNASer(UCN) G7444A mutation in the development of maternally inherited non-syndromic deafness. Methods: PCR amplification of mitochondrial 12S rRNA, mitochondrial tRNASer(UCN) and GJB2 gene of 2 650 Chinese Han non-syndromic deafness subjects. The proband and family members of 11 Chinese Han pedigrees with mitochondrial tRNASer(UCN) G7444A mutation underwent audiological testing, deafness associated mutational hot spots screening and pedigree assessment. Results: Among the 2 650 Han Chinese non-syndromic deafness subjects, 22 patients belonging to 11 pedigrees carried mitochondrial tRNASer(UCN) G7444A mutation, account for 0.7%. Number of pedigree carry both mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G, mitochondrial 12S rRNA C1494T or GJB2 c.235delC mutation were 3, 1, 2 respectively. Clinical data showed that there were huge difference in the severity of hearing loss, age of onset and penetrance among these 11 Chinese Han non-syndromic deafness pedigrees. The average penetrance of these pedigrees carrying mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G, C1494T or GJB2 c.235delC mutation were 29.4%, 42.9% and 19.0% respectively. The average penetrance of 4 pedigrees carrying the mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G or C1494T mutation is significantly higher than that of carry mitochondrial tRNASer(UCN) G7444A mutation, it was 14.0%. Conclusion: Mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G or C1494T mutations may co-modulate the variable penetrance and expressivity of deafness among these Han Chinese non-syndromic pedigrees.
