Molecular bases of hearing loss in multi-systemic mitochondrial cytopathy.
OBJECTIVE
Hearing loss is a common clinical feature in classic mitochondrial syndromes. The purpose of this study was to evaluate the diverse molecular etiologies and natural history of hearing loss in multi-systemic mitochondrial cytopathies and the possible correlation between degree of hearing loss and neurological phenotype.


METHODS
In this retrospective study we evaluated the clinical features and molecular bases of hearing loss associated with multi-systemic mitochondrial cytopathy. Forty-five patients with sensorineural hearing loss and definite diagnosis of mitochondrial cytopathy according to the published diagnostic criteria were studied.


RESULTS
The sensorineural hearing loss was progressive and for the most part symmetrical with involvement of the higher frequencies. Both cochlear and retrocochlear involvement were found in this cohort. No correlation was found between the degree of hearing loss and the number and severity of neurological manifestations. Deleterious mtDNA point mutations of undisputed pathogenicity were identified in 18 patients. The A3243G mutation was the most frequently encountered among this group. MtDNA depletion, over-replication, and multiple deletions were found in further 11 cases.


CONCLUSIONS
This study reveals an expanding spectrum of mtDNA abnormalities associated with hearing loss. No correlation was found between the degrees of hearing loss and the severity of neurological manifestations.
Scaglia
Fernando
F
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Hsu
Chang-Hung
CH
Kwon
Haeyoung
H
Bai
Ren-Kui
RK
Perng
Cherng-Lih
CL
Chang
Hua-Mei
HM
Dai
Pu
P
Smith
E O'Brian
EO
Whiteman
David A H
DA
Feigenbaum
Annette
A
Gropman
Andrea
A
Wong
Lee-Jun C
LJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation
D004272:DNA, Mitochondrial