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Clinical Genetics
Article . 2024 . Peer-reviewed
License: CC BY
Data sources: Crossref
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Non‐syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity

Authors: Siying Lin; Anthony G. Robson; Dorothy A. Thompson; Karolina M. Stepien; Robin Lachmann; Emma Footitt; Ola Czyz; +8 Authors

Non‐syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity

Abstract

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.

Country
United Kingdom
Keywords

Adult, Male, Adolescent, Genotype, Multiple Sulfatase Deficiency Disease, Sulfatases/genetics, SUMF1, Article, MSD, Young Adult, Retinal Dystrophies, Leukocytes, Humans, Oxidoreductases Acting on Sulfur Group Donors, Oxidoreductases Acting on Sulfur Group Donors/genetics, Alleles, Retinal Dystrophies/genetics, Whole Genome Sequencing, Leukocytes/pathology, Middle Aged, retinal dystrophies, Phenotype, Mutation, lysosomal storage disorder, multiple sulfatase deficiency, Multiple Sulfatase Deficiency Disease/genetics, Female, Sulfatases

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Top 10%
Average
Average
Green
hybrid