De novo mutation in ATP6V1B2 impairs lysosome acidification and causes dominant deafness-onychodystrophy syndrome

Dominant deafness-onychodystrophy syndrome (DDOD syndrome; MIM 124480) is characterized mainly by congenital sensorineural hearing loss accompanied by dystrophic or absent nails. Prominent differences between DDOD syndrome and DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures; MIM 220500) are the intellectual disability and seizure aspects of DOORS1. TBC1D24 mutations were recently identified as a cause of DOORS syndrome2. To date, six families with DDOD syndrome in various ethnic populations have been reported3. However, the molecular etiology of DDOD remains unknown. We collected three Chinese DDOD pedigrees during the past two years. The probands displayed identical phenotypes including severe congenital sensorineural hearing loss, absence of nails and aplasia of the middle phalanx in the fifth fingers (Figure 1A and 1B). None showed inner ear malformation and intellectual disability. All three individuals had unilateral cochlea implantation at the ages of 2.5, 2 and 18 years, respectively. The successful language rehabilitation in the DDOD probands further confirmed their normal mental development.