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In an online ahead of print issue of the journal Human Molecular Genetics researchers from the Departments of Human Genetics, Ophthalmology, and Neurology in the Radboudumc in Nijmegen and from Israel report on the identification of a novel gene (HGSNAT) to be implicated in persons with non-syndromic severe visual impairment. The HGSNAT gene codes for a lysosomal protein. Lysosomes can be considered ‘recycle factories’ that process ‘waste proteins’ into new cellular components in all human tissues. It was already known that severe mutations in HGSNAT can cause mucopolysaccharidosis type IIIC (MPS IIIC), a severe and lethal syndromic disorder. Next to severe cognitive and/or neurological deterioration patients with MPS IIIC develop retinitis pigmentosa, a disease of the retina that leads to severe visual impairment.


Using next generation sequencing Dr. L. Haer-Wigman identified mild mutations in the HGSNAT gene in a Dutch family with three siblings affected by  retinitis pigmentosa, who did not show any of the other MPS IIIC symptoms. Similar findings were made in two Israeli families. HGSNAT activity studies showed that the non-syndromic patients had lower HGSNAT activity levels compared to controls, but higher activity levels compared to patients with MPS IIIC. The authors therefore hypothesize that the retina requires higher HGSNAT activity levels to maintain normal function, compared to other tissues that are associated with MPS IIIC, such as the brain. Similar results have recently been published for two other lysosomal genes, i.e. CLN3 and MFSD8, thereby establishing a new disease mechanism for non-syndromic inherited retinal diseases.


Non-syndromic Retinitis Pigmentosa due to Mutations in the Mucopolysaccharidosis Type IIIC Gene, Heparan-Alpha-Glucosaminide N-Acetyltransferase (HGSNAT).

Haer-Wigman L, Newman H*, Leibu R*, Bax N*M, Baris HN, Rizel L, Banin E, Massarweh A, Roosing S, Lefeber DJ, Zonneveld-Vrieling MN, Isakov O, Shomron N, Sharon D, den Hollander AI, Hoyng CB, Cremers FPM, Ben-Yosef T. Human Molecular Genetics; 10.1093/hmg/ddv118. *Shared authorships.


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Visual defect in patient with retinitis pigmentosa

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