DBQD2_XYLT1
- Gene
- XYLT1
- Disease
- DBQD2
- Inheritance
- AR
- Classification
- Moderate
- Total Score
- 8.5
- Publications Reviewed
- 2
- Publication Span
- 4.83 years
- Last Updated
- 08/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Autosomal recessive DBQD2/Baratela-Scott syndrome is associated with biallelic XYLT1 pathogenic variants, including a promoter/5' UTR GGC repeat expansion that causes XYLT1 exon 1 hypermethylation and transcriptional silencing. XYLT1 encodes xylosyltransferase I, which initiates proteoglycan glycosaminoglycan-chain biosynthesis; gene-level patient fibroblast studies show reduced XYLT1 expression and impaired cellular proteoglycan synthesis, supporting disease relevance but not always repeat-specific mechanism.
Genetic evidence
Total: 6
| Singular Evidence | Probands | PMID:30554721 | 6 | Twelve affected individuals from 10 unrelated BSS/DBQD2-spectrum families were investigated; XYLT1 pathogenic alleles included biallelic sequence/CNV variants and a promoter/5' UTR GGC repeat expansion associated with exon 1 hypermethylation. The methylated/expanded allele accounted for 50% of disease alleles and segregated in trans with sequence variants or deletions where assessable. |
1 rows
Experimental evidence
Total: 2.5
| Function | Biochemical function | PMID:24581741 | 0.5 | Gene-level, not tandem-repeat-specific: XYLT1 encodes XT-I, which catalyzes the first step of proteoglycan biosynthesis by transferring xylose to serine residues of proteoglycan core proteins to initiate GAG-chain synthesis. |
| Function | Protein interaction | PMID:24581741 | 0.5 | PMID 24581741 describes XT-I enzymatic function and effects on proteoglycan biosynthesis. |
| Function | Regulatory impact | PMID:24581741 | 1.5 | Gene-level, not tandem-repeat-specific: qPCR in two patient fibroblast lines with truncating XYLT1 variants showed a dramatic reduction of XYLT1 cDNA; XYLT2 expression was decreased compared with one control, whereas B4GALT7 was not affected. |
3 rows
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.