These results seem to indicate that conductive hearing loss and hyperopia may appear randomly in patients with NOG mutations; whereas, in contrast with most NOG mutations that have been reported in kindreds with SYM1 and SYNS1, the mutations observed in families with stapes ankylosis without SYM1 are predicted to disrupt the cysteine-rich C-terminal domain [21,22]. Here, NOG is linked to ankylosis.