Expanding the phenotypic and genotypic spectrum of patients with HGSNAT-related retinopathy.

Background: Variants in HGSNAT have historically been associated with syndromic mucopolysaccharidosis type IIIC (MPSIIIC) but more recent studies demonstrate cases of HGSNAT-related non-syndromic retinitis pigmentosa. We describe and expand the genotypic and phenotypic spectrum of this disease.

Materials and methods: This is a retrospective, observational, case series of 11 patients with pericentral retinitis pigmentosa due to variants in HGSNAT gene without a syndromic diagnosis of MPSIIIC. We reviewed ophthalmologic data extracted from medical records, genetic testing, color fundus photos, fundus autofluorescence (FAF), and optical coherence tomography (OCT).

Results: Of the 11 patients, the mean age was 52 years (range: 26-78). The mean age of ophthalmologic symptoms onset was 45 years (range: 15-72). The visual acuity varied from 20/20 to 20/80 (mean 20/30 median 20/20). We described five novel variants in HGSNAT: c.715del (p.Arg239Alafs *37), c.118 G>A (p.Asp40Asn), c.1218_1220delinsTAT, c.1297A>G (p.Asn433Asp), and c.1726 G>T (p.Gly576*).

Conclusions: HGSNAT has high phenotypic heterogeneity. Data from our cohort showed that all patients who had at least one variant of c.1843 G>A (p.Ala615Thr) presented with the onset of ocular symptoms after the fourth decade of life. The two patients with onset of ocular symptoms before the fourth decade did not carry this variant. This may suggest that c.1843 G>A variant is associated with a later onset of retinopathy.