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The ND4 G11696A mutation may influence the phenotypic manifestation of the deafness-associated 12S rRNA A1555G mutation in a four-generation Chinese family - PubMed

  • ️Mon Jan 01 2007

Case Reports

. 2007 Oct 26;362(3):670-6.

doi: 10.1016/j.bbrc.2007.08.034. Epub 2007 Aug 15.

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Case Reports

The ND4 G11696A mutation may influence the phenotypic manifestation of the deafness-associated 12S rRNA A1555G mutation in a four-generation Chinese family

Zhisu Liao et al. Biochem Biophys Res Commun. 2007.

Abstract

We report here the clinical, genetic and molecular characterization of a large Han Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. The penetrance of hearing loss (affected matrilineal relatives/total matrilineal relatives) in this pedigree was 53%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrance of hearing loss in this pedigree was 42%. These matrilineal relatives exhibited a wide range of severity of hearing loss, varying from profound to normal hearing. Furthermore, these affected matrilineal relatives shared some common features: bilateral hearing loss of high frequencies and symmetries. Sequence analysis of mitochondrial DNA (mtDNA) in the pedigree identified the homoplasmic 12S rRNA A1555G mutation and other 35 variants belonging to Eastern Asian haplogroup D4. Of these, the V313I (G11696A) mutation in ND4 was associated with vision loss. However, the extremely low penetrance of visual loss, and the mild biochemical defect and the presence of one/167 Chinese controls indicted that the G11696A mutation is itself not sufficient to produce a clinical phenotype. Thus, the G11696A mutation may act in synergy with the primary deafness-associated 12S rRNA A1555G mutation in this Chinese family, thereby increasing the penetrance and expressivity of hearing loss in this Chinese pedigree.

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Figures

Figure 1
Figure 1. A four-generation Han Chinese pedigree with aminoglycoside-induced and nonsyndromic hearing impairment

Hearing-impaired individuals are indicated by filled symbols. Arrowhead denotes proband. Asterisks denote individuals who had a history of exposure to aminoglycosides.

Figure 2
Figure 2. Air conduction audiogram of three members in the Chinese family

Symbols: X-left, O-right ear.

Figure 3
Figure 3. Identification and qualification of A1555G and G11696A mutations

Partial sequences chromatograms of 12S rRNA and ND4 genes from two matrilineal relatives and one married-in Chinese control.

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