Curation DBQD2 XYLT1

Gene XYLT1
Disease DBQD2
Inheritance AR
Score

6 + 2.5 = 8.5 / 18

Genetic + experimental = total
Classification
0
18
Refuted
Moderate
Definitive
Last Updated 08/18/2025
Pubs Reviewed 2
Publication Span 4.83 years
Publication Interval 4.83 years
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.

All criTRia Curations Locus Page

Genetic evidence

Total: 6

Category
Type
Citation
Score
Details
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.

Experimental evidence

Total: 2.5

Category
Type
Citation
Score
Details
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.
Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.