Figure 1.
Localization of 20 KCNQ4 mutations reported in previous studies in the protein.
The 6 transmembrane domains (S1–S6) and the P-loop, located between S5 and S6, are shown. 5 mutations are concentrated in a narrow P-loop range. Mutations with pink and blue shadows; possible mutations detected in this study. Blue indicates novel mutations. Original schema is modified from Mencía A (2008) [14].
Table 1.
KCNQ4 mutations found in this study together with previously reported mutations.
Figure 2.
The haplotypes around c.211delC mutation of six families constructed using SNPs are shown.
Each column shows an affected allele. Each base is defined by pure segregation analysis in the family. Allele frequencies of SNPs are derived from HapMap JPT+CHB samples. Families 2, 5, 10, and 13 shared a large common region of about more than 1 Mb in their haplotypes (blue). Abbreviation: Fm, Family.
Table 2.
Clinical features of affected family members associated with KCNQ4 mutations found in this study.
Figure 3.
Overlapping audiograms from the better ear for each genotype.
In cases of W276S, c.211delC, or V230E, light colored audiograms (green, blue, red) were from individuals aged 19 and under. Dark colored audiograms (green, blue, red) were from the patients aged 20–49 years old, and deep colored audiograms (green, blue, red) are from the patients in their 50 s and over. In family #13 with c.211delC, (*) a six-year-old boy's hearing is normal in spite of having the mutation.
Figure 4.
Detailed progression analysis in each frequency.
A single audiogram (the better ear) from a single patient was plotted. Gradual progression is characterized regardless of frequency. Average progressive rates of hearing loss (db/year) for the patients with c.211delC, for 125 (0.15) and 250 Hz (0.078) were significantly stable compared to the other two mutations (ANCOVA: p<0.05) and they had milder hearing loss at 500 and 1 KHz (ANCOVA: p<0.05). In contrast, at 4 KHz and 8 KHz, patients with V230E mutations had milder hearing loss compared to the other two mutations (ANCOVA: p<0.05). Each color (green, blue, red) indicates W276S, c.211delC, or V230E, respectively.