ClinVar

In affected children from 2 consanguineous Israeli Druze families with congenital disorder of glycosylation type Im (CDG1M; 610768), Lefeber et al. (2011) identified homozygosity for a 1222C-G transversion in the DOLK gene, resulting in a his408-to-asp (H408D) substitution at a highly conserved residue. The mutation was not found in more than 1,000 Caucasian controls or in the 1000 Genomes Project. Although the families resided in 2 different villages in northern Israel and were believed to be unrelated, the presence of an identical 5-Mb haplotype and mutation suggested a founder event among these Druze kindreds. Functional analysis in temperature-sensitive underglycosylated sec59 yeast cells demonstrated that the mutant protein failed to restore glycosylation to the same extent as wildtype. Cardiac tissue from a patient's explanted heart showed reduced O-mannosylation of alpha dystroglycan (128239) with concomitant functional loss of its laminin (see 150320)-binding capacity.