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

BACKGROUND: Multiple sulfatase deficiency (MSD) (MIM#272200) is an ultra-rare autosomal recessive lysosomal storage disorder caused by mutation of the Sulfatase Modifying Factor 1 (SUMF1) gene. METHODS: Herein, we report an eight-year-old boy with a late infantile form of multiple sulfatase deficiency. A combination of copy-number variation sequencing (CNV-seq) and whole-exome sequencing (WES) were used to analyze the genetic cause for the MSD patient. RESULTS: Our results, previously not seen in China, show a novel compound heterozygous mutation with one allele containing a 240.55 kb microdeletion on 3p26.1 encompassing the SETMAR gene and exons 4-9 of the SUMF1 gene, and the other allele containing a novel missense mutation of c.671G>A (p.Arg224Gln) in the SUMF1 gene. Both were inherited from the proband's unaffected parents, one from each. Bioinformatics analyses show the novel variation to be "likely pathogenic." SWISS-MODEL analysis shows that the missense mutation may alter the three-dimensional (3D) structure. CONCLUSIONS: In summary, this study reported a novel compound heterozygous with microdeletion in SUMF1 gene, which has not been reported in China. The complex clinical manifestations of MSD may delay diagnosis; however, molecular genetic analysis of the SUMF1 gene can be performed to help obtain an early diagnosis.