» Articles » PMID: 15146462

Molecular and Functional Analysis of SUMF1 Mutations in Multiple Sulfatase Deficiency

Abstract

Multiple sulfatase deficiency (MSD) is a rare disorder characterized by impaired activity of all known sulfatases. The gene mutated in this disease is SUMF1, which encodes a protein involved in a post-translational modification at the catalytic site of all sulfatases that is necessary for their function. SUMF1 strongly enhances the activity of sulfatases when coexpressed with sulfatase in Cos-7 cells. We performed a mutational analysis of SUMF1 in 20 MSD patients of different ethnic origin. The clinical presentation of these patients was variable, ranging from severe neonatal forms to mild phenotypes showing mild neurological involvement. A total of 22 SUMF1 mutations were identified, including missense, nonsense, microdeletion, and splicing mutations. We expressed all missense mutations in culture to study their ability to enhance the activity of sulfatases. Of the predicted amino acid changes, 11 (p.R349W, p.R224W, p.L20F, p.A348P, p.S155P, p.C218Y, p.N259I, p.A279V, p.R349Q, p.C336R, p.A177P) resulted in severely impaired sulfatase-enhancing activity. Two (p.R345C and p.P266L) showed a high residual activity on some, but not all, of the nine sulfatases tested, suggesting that some SUMF1 mutations may have variable effects on the activity of each sulfatase. This study compares, for the first time, clinical, biochemical, and molecular data in MSD patients. Our results show lack of a direct correlation between the type of molecular defect and the severity of phenotype.

Citing Articles

Complementarity of biomarker screening and genetic analyses based on the case of an attenuated multiple sulfatase deficiency.

Lipinski P, Lugowska A, Pollak A, Ploski R, Tylki-Szymanska A J Appl Genet. 2025; .

PMID: 39776369 DOI: 10.1007/s13353-024-00936-2.


Hematopoietic stem cell gene therapy improves outcomes in a clinically relevant mouse model of multiple sulfatase deficiency.

Pham V, Tricoli L, Hong X, Wongkittichote P, Castruccio Castracani C, Guerra A Mol Ther. 2024; 32(11):3829-3846.

PMID: 39169621 PMC: 11573602. DOI: 10.1016/j.ymthe.2024.08.015.


Late infantile form of multiple sulfatase deficiency with a novel missense variant in the SUMF1 gene: case report and review.

Sheth J, Shah S, Datar C, Bhatt K, Raval P, Nair A BMC Pediatr. 2023; 23(1):133.

PMID: 36959582 PMC: 10037891. DOI: 10.1186/s12887-023-03955-w.


The Effects of N-Acetyl-L-Leucine on the Improvement of Symptoms in a Patient with Multiple Sulfatase Deficiency.

Saberi-Karimian M, Houra M, Jamialahmadi T, Sarvghadi P, Nikbaf M, Akhlaghi S Cerebellum. 2022; 22(6):1250-1256.

PMID: 36482027 PMC: 9735006. DOI: 10.1007/s12311-022-01504-2.


Genetic analysis of a novel SUMF1 variation associated with a late infantile form of multiple sulfatase deficiency.

Zhang J, Ma D, Liu G, Zeng H, Wang Y, Luo C J Clin Lab Anal. 2022; 36(12):e24786.

PMID: 36441600 PMC: 9756991. DOI: 10.1002/jcla.24786.