Mutation screening and burden analysis of GLT8D1 in Chinese patients with amyotrophic lateral sclerosis.

The glycosyltransferase 8 domain containing 1 (GLT8D1) gene was identified to be an amyotrophic lateral sclerosis (ALS)-causative gene via pedigree cosegregation and burden analysis. In the present study, 977 Chinese sporadic ALS (sALS) cases and 47 Chinese familial ALS (fALS) cases underwent whole-exome sequencing. Rare variants with minor allele frequency <0.1% in GLT8D1 were analyzed. One likely pathogenic variant in the exon 4 was identified in a fALS case and validated within the family. Moreover, 3 rare variants of uncertain significance in 4 patients with sALS and 1 rare variant of uncertain significance in 1 patient with fALS were also identified. Furthermore, by using the East Asian controls from the gnomAD database, there was no significant enrichment of rare variants of GLT8D1 at the whole-gene level or the exon 4-specific level in Chinese patients with sALS. In conclusion, cosegregation findings further support the pathogenic role of GLT8D1 in fALS. However, no pathogenic mutation and no enrichment of rare variants were found in patients with sALS, which implies that GLT8D1 may not play a role in Chinese patients with sALS.