Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.

中文翻译：

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HGSNAT 中的序列变异导致非综合征性视网膜病变个体的遗传和临床研究，该基因与 Sanfilippo C 粘多糖贮积症相关。

据报道，基因HGSNAT（乙酰肝素-α-氨基葡萄糖N-乙酰转移酶）的致病变异是两种不同的隐性疾病的基础，这取决于特定的基因型，黏多糖贮积症 IIIC 型 (MPSIIIC)——一种严重的儿童期发病溶酶体贮积症和成人发病的非综合征性视网膜色素变性（RP）。在这里，我们描述了迄今为止最大的HGSNAT相关非综合征 RP 患者队列，并描述了他们的视网膜表型、白细胞酶活性和可能的​​致病基因型。我们确定了双等位基因HGSNAT17 个人（15 个家庭）的变异是其 RP 的可能原因。没有人表现出任何其他 MPSIIIC 症状。所有人的白细胞中的 HGSNAT 酶活性都有轻微但显着的降低。视网膜状况一般为迟发性，表现为黄斑旁视网膜同心区域进行性退化，保留但视网膜电图反应减弱。症状、电生理学和成像表明杆状光感受器是最初受损的细胞。HGSNAT酶促检测有助于解决兼容患者的诊断难题。我们鉴定了七种新的序列变体 [p.(Arg239Cys); p.（Ser296Leu）；p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543-2A>C; c.1708delA]，其中三个被认为是视网膜疾病特异性等位基因。最普遍的视网膜疾病特异性等位基因 p.(Ala615Thr) 分别在 8 个和 5 个个体（7 个和 4 个家庭）中观察到杂合子或纯合子。一个家庭中的两个兄弟姐妹，虽然HGSNAT基因座相同，但视网膜疾病不一致，这表明反式作用遗传或环境改变因素的影响。