For discussion of the arg401-to-ter (R401X) mutation in the NGLY1 gene that was found in compound heterozygous state in a patient with congenital disorder of deglycosylation (CDDG1; 615273) by Need et al. (2012), see 610661.0001.
In 5 patients from 3 families with CDDG1, Enns et al. (2014) identified a homozygous c.1201A-T transversion in exon 8 of the NGLY1 gene, resulting in an arg401-to-ter (R401X) substitution. All of the patients were Caucasian and of European descent, suggesting the possibility of a founder mutation. The R401X mutation was found in 2 of 8,598 chromosomes of European ancestry and once among African American chromosomes in the Exome Variant Server database.
The R401X mutation was the most common among the 12 individuals studied by Lam et al. (2017), accounting for 7 alleles.
In 3 unrelated patients with CDDG1, Panneman et al. (2020) identified the R401X mutation in the NGLY1 gene: patient 2 was homozygous for the mutation, whereas patient 1 also had a c.849T-G transversion, resulting in a cys283-to-trp (C283W; 610661.0006) substitution, and patient 3 had a c.1067A-G transition, resulting in a glu356-to-gly (E356G; 610661.0007) substitution. The mutations were identified by whole-exome sequencing, and the parents in all families were confirmed to be carriers. Western blot analysis in patient muscle tissue and fibroblasts showed absence of NGLY1 protein expression.
