Inherited Nonsyndromic Hearing Loss: An Audiovestibular Study in a Large Family With Autosomal Dominant Progressive Hearing Loss Related to DFNA2

A Dutch family with progressive sensorineural hearing impairment linked to the DFNA2 region

“…A similar trend was detected in two previously reported Dutch families [10,15]. Systematic comparison of the findings in our present DFNA2 family uncovered a higher annual threshold increase (1 dB/yr) and lower mean offset thresholds values (13-15 dB; 0.25 kHz-2 kHz) in two closely similar families [11,16]. Our present family shows a higher offset but slightly less rapid progression in hearing loss.…”

“…Our present family shows a higher offset but slightly less rapid progression in hearing loss. As a result, estimating from regression lines at age 43 years (i.e., the average age in the present family), the average threshold at each frequency was almost similar within 3 dB [16], while in the other Dutch family [10] it was on average only some 4 dB higher. The previously reported Indonesian family showed a predominance of higher thresholds by middle age, whereas additional data indicated postlingual onset and excessive progression in the first two decades of life [1,2].…”

A KCNQ4 c.546C>G Genetic Variant Associated with Late Onset Non-Syndromic Hearing Loss in a Taiwanese Population

“…In addition, this study demonstrated the correlation between the KCNQ4 variant and the fracture of lower limbs. In a prior family study, no vestibular problem was observed in families with pathogenic variants of KCNQ4 [33]. Our results indicated that 16.7% of the c.546C>G variant carriers had previously sought medical treatment due to vertigo.…”

Audioprofile-Directed Successful Mutation Analysis in a DFNA2/KCNQ4 (p.Leu274His) Family

“…There was a striking similarity (Fig 3) between the audioprofile of the present family Dutch VI and the audioprofiles of the other traits caused by various KCNQ4 mutations affecting the channel pore region. These KCNQ4 mutations are p.Leu274His (family Dutch III 15,23 ), the hotspot mutation p.Trp276Ser (the mean ARTA for 4 different traits is shown 6,13,16,18 In all affected family members, the c.821T>A (p.Leu274His) mutation was detected. The sequence chromatogram is shown in Fig 4. This mutation is believed to be pathogenic because it occurs in the P-loop of the protein and therefore probably inter-feres with pore formation in the final protein complex.…”

“…In Fig 3, the ARTA for this family (family Dutch VI) is shown and ARTAs are presented for families with the same mutation (top right panel) and other mutations in KCNQ4. 5,[9][10][11][12][13][14][15][16][17][18] Some of the reported mutations 7,[19][20][21] have not been included, because we were unable to derive reliable ARTAs.…”