{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:17:43Z","timestamp":1791339463368,"version":"4.3.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012618","name":"National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001285","name":"UCL Institute of Ophthalmology, University College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001285","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206619\/Z\/17\/Z"],"award-info":[{"award-number":["206619\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenic variants in the gene <jats:italic>HGSNAT<\/jats:italic> (heparan\u2010<jats:italic>\u03b1<\/jats:italic>\u2010glucosaminide <jats:italic>N<\/jats:italic>\u2010acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)\u2014a severe childhood\u2010onset lysosomal storage disorder, and adult\u2010onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to\u2010date of <jats:italic>HGSNAT<\/jats:italic>\u2010associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic <jats:italic>HGSNAT<\/jats:italic> 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\u2010onset, 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. <jats:italic>HGSNAT<\/jats:italic> 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\u20102A&gt;C; c.1708delA], three of which were considered to be retina\u2010disease\u2010specific alleles. The most prevalent retina\u2010disease\u2010specific 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 <jats:italic>HGSNAT<\/jats:italic> locus, but discordant for retinal disease, suggest the influence of trans\u2010acting genetic or environmental modifying factors.<\/jats:p>","DOI":"10.1002\/ajmg.c.31822","type":"journal-article","created":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T06:50:14Z","timestamp":1596869414000},"page":"631-643","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in <scp><i>HGSNAT<\/i><\/scp>, the gene associated with Sanfilippo C mucopolysaccharidosis"],"prefix":"10.1002","volume":"184","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9848-1302","authenticated-orcid":false,"given":"Elena R.","family":"Schiff","sequence":"first","affiliation":[{"name":"Genetics Service Moorfields Eye Hospital  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malena","family":"Daich Varela","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony G.","family":"Robson","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology  London UK"},{"name":"Department of Electrophysiology Moorfields Eye Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Pierpoint","sequence":"additional","affiliation":[{"name":"Genetics Service Moorfields Eye Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rola","family":"Ba\u2010Abbad","sequence":"additional","affiliation":[{"name":"Genetics Service Moorfields Eye Hospital  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savita","family":"Nutan","sequence":"additional","affiliation":[{"name":"North Thames Genomic Laboratory Hub Great Ormond Street NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadih M.","family":"Zein","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Ullah","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laryssa A.","family":"Huryn","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari","family":"Tuupanen","sequence":"additional","affiliation":[{"name":"Blueprint Genetics  Espoo Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar A.","family":"Mahroo","sequence":"additional","affiliation":[{"name":"Genetics Service Moorfields Eye Hospital  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"},{"name":"Section of Ophthalmology King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Michaelides","sequence":"additional","affiliation":[{"name":"Genetics Service Moorfields Eye Hospital  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Burke","sequence":"additional","affiliation":[{"name":"Enzyme Unit, Chemical Pathology, Paediatric Laboratory Medicine Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Harvey","sequence":"additional","affiliation":[{"name":"Enzyme Unit, Chemical Pathology, Paediatric Laboratory Medicine Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-7888","authenticated-orcid":false,"given":"Gavin","family":"Arno","sequence":"additional","affiliation":[{"name":"Genetics Service Moorfields Eye Hospital  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"},{"name":"North Thames Genomic Laboratory Hub Great Ormond Street NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Hufnagel","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function branch National Eye Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Webster","sequence":"additional","affiliation":[{"name":"Genetics Service Moorfields Eye Hospital  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1629"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3090688"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.12.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.119"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes8100256"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21286"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007434"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20986"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-59"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.19-27761"},{"issue":"13","key":"e_1_2_8_12_1","first-page":"3742","article-title":"Non\u2010syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, Heparan\u2010alpha\u2010glucosaminide N\u2010acetyltransferase (HGSNAT)","volume":"24","author":"Haer\u2010Wigman L.","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/508294"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/35.7.1472"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2017.1401"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e31822059ae"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.283"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004015"},{"key":"e_1_2_8_19_1","first-page":"616544","article-title":"Nonsyndromic retinitis pigmentosa caused by two novel variants in the HGSNAT gene in a Chinese family","volume":"73","author":"Long Y.","year":"2020","journal-title":"Ophthalmic Genetics"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23752"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-014-9473-7"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-019-09730-6"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/302926"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.09.011"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-018-9645-y"},{"key":"e_1_2_8_26_1","first-page":"k1687","article-title":"The 100 000 genomes project: Bringing whole genome sequencing to the NHS","volume":"361","author":"Turnbull C.","year":"2018","journal-title":"BMJ 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Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.31822","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.c.31822","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.31822","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T05:28:08Z","timestamp":1693546088000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.31822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1002\/ajmg.c.31822"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.31822","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"value":"1552-4868","type":"print"},{"value":"1552-4876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]},"assertion":[{"value":"2020-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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