Submission Details

X-linked

09/18/2019

The SLC35A2 gene is located on chromosome X at Xp11.23 and encodes the solute carrier family 35 member A2 protein, which is associated with transporting nucleotide sugars, especially UDP-galactose, from the cytosol into Golgi vesicles. SLC35A2 was first reported in relation to X-linked dominant congenital disorders of glycosylation in 2013 (23561849: Ng et al. 2013). Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least six unique variants have been reported in humans, including four loss of function variants, one in-frame deletion, and one missense variant (24115232: Kodera et al. 2013; 31231989: Miyamoto et al. 2019; 30817854: Ng et al. 2019). Patients showed varying degrees of neurological symptoms, particularly epilepsy, developmental delay, and intellectual disability. Other features included hypotonia, microcephaly, abnormal brain imaging results, skeletal abnormalities, facial dysmorphism, and ocular abnormalities (30817854: Ng et al. 2019). More evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease relationship is supported by the biochemical function of the SLC35A2 protein in transporting nucleotide sugars, especially UDP-galactose, from the cytosol into Golgi vesicles where glycosyltransferases function (11319223: Oelmann et al. 2001). Defects in galactose transport were shown in fibroblasts from ten different patients (30817854: Ng et al. 2019). In summary, the SLC35A2 gene is definitively associated with X-linked dominant congenital disorders of glycosylation.

24115232 31231989 30817854 11319223