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Hearing Loss in Mitochondrial Disorders
Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DC 2007, USA 20007
aC-H.H. and H.K. contributed equally to this study. bCurrent address: Department of Neurology (C-H.H.) and Division of Clinical Pathology (C-L.P.), Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. cCurrent address: Department of Otolaryngology, 301 General Hospital, Beijing, People's Republic of China. Address for correspondence: Lee-Jun C. Wong, Ph.D., Institute for Molecular and Human Genetics, Georgetown University Medical Center, M4000, 3800 Reservoir Rd., NW, Washington, DC 20007. Voice: 202-444-0760; fax: 202-444-1770. wonglj{at}georgetown.edu
Hearing loss is a common clinical feature in mitochondria-syndrome disorders. The underlining molecular etiology of hearing loss has not been fully investigated. In this study, 83 patients with mitochondrial syndromic hearing loss were evaluated clinically and their blood and tissue samples were examined molecularly. Using modified Walker's criteria, 31, 31, 14, and 7 patients had been classified as having definite, probable, possible, and unlikely diagnosis of mitochondrial disease, respectively. Deleterious mtDNA point mutations and/or abnormal mtDNA content or multiple deletions were identified in 20 patients with definite diagnosis and 2 patients with probable diagnosis. In addition to known, undisputed pathogenic mutations, several novel mutations believed to be clinically significant were found. Furthermore, abnormal mtDNA content and mtDNA deletions were found in some of the cases. Evaluation of clinical and diagnostic features associated with hearing loss revealed that cardiomyopathy, lactic acidosis, deficient respiratory chain enzyme complex activities, histochemical and ultrastructural abnormalities in mitochondria, and abnormal brain imaging results occurred significantly more frequently in patients with mtDNA alterations than in those without. This study revealed that the majority of the mtDNA defects in patients with mitochondrial syndromic hearing loss affect the overall mitochondrial gene expression.
Key Words: multisystemic mitochondrial disorder • deafness • maternally inherited deafness • syndromic hearing loss
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