NATURE GENETICS, vol.37, no.12, pp.1312-1314, 2005 (SCI-Expanded)
SIL1 ( also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP ( also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sjogren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sjogren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.