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

ABSTRACT

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.

KEYWORDS:

• Lysosomal storage disorders
• HGSNAT
• Sanfilippo syndrome
• retinitis pigmentosa
• rare disease

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2023.2245035.

Additional information

Funding

L.A.E. Foundation Fighting Blindness Career Development Award.P.Y. Supported by grant P30 EY010572 from the National Institutes of Health (Bethesda, MD), and by unrestricted departmental funding from Research to Prevent Blindness (New York, NY).M.E.P. Unrestricted Grant from Research to Prevent Blindness (CEI).NIH P30 EY010572 (CEI).