Lin, Siying;
Robson, Anthony G;
Thompson, Dorothy A;
Stepien, Karolina M;
Lachmann, Robin;
Footitt, Emma;
Czyz, Ola;
... Webster, Andrew R; + view all
(2024)
Non-syndromic retinal dystrophy associated with biallelic
variation of SUMF1 and reduced leukocyte sulfatase activity.
Clinical Genetics
10.1111/cge.14573.
(In press).
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Abstract
Biallelic variants in SUMF1 are associated with multiple sulfatase deficiency (MSD), a rare lysosomal storage disorder typically diagnosed in early infancy or childhood, marked by severe neurodegeneration and early mortality. We present clinical and molecular characterisation of three unrelated patients aged 13 to 58 years with milder clinical manifestations due to SUMF1 disease variants, including two adult patients presenting with apparent non‐syndromic retinal dystrophy. Whole genome sequencing identified biallelic SUMF1 variants in all three patients; Patient 1 homozygous for a complex allele c.[290G>T;293T>A]; p.[(Gly97Val);(Val98Glu)], Patient 2 homozygous for c.866A>G; p.(Tyr289Cys), and Patient 3 compound heterozygous for c.726‐1G>C and p.(Tyr289Cys). Electroretinography indicated a rod‐cone dystrophy with additional possible inner retinal dysfunction in all three patients. Biochemical studies confirmed reduced, but not absent, sulfatase enzyme activity in the absence of extra‐ocular disease (Patient 1) or only mild systemic disease (Patients 2, 3). These cases are suggestive that non‐null SUMF1 genotypes can cause an attenuated clinical phenotype, including retinal dystrophy without systemic complications, in adulthood.
| Type: | Article |
|---|---|
| Title: | Non-syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/cge.14573 |
| Publisher version: | http://dx.doi.org/10.1111/cge.14573 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd |
| Keywords: | lysosomal storage disorder, MSD, multiple sulfatase deficiency, retinal dystrophies, SUMF1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10193465 |
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