OPA1 and deafness: This variant is a common cause of isolated autosomal DOA associated with deafness, as is the recurrent p.R500H mutation in OPA1. WFS1 encodes the wolframin, a transmembrane endoplasmic reticulum protein that plays an essential role in calcium homeostasis and interorganelle cross-talk at mitochondria-associated membranes (33, 39), highlighting the important role of these structures in the pathophysiology of IONs.