On this page
DSE
dermatan sulfate epimerase
DSE is located on the long (q) arm of chromosome 6, at band 6q22.1. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 6 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The DSE gene, located on chromosome 6, encodes dermatan sulfate epimerase, an enzyme responsible for converting specific sugar residues during the biosynthesis of dermatan sulfate. Dermatan sulfate is a glycosaminoglycan found throughout the extracellular matrix, the structural scaffold surrounding cells in connective tissue. This molecule contributes to the mechanical properties of skin, tendons, blood vessels, and other tissues.
Pathogenic variants in DSE disrupt the normal assembly of dermatan sulfate, compromising the structural integrity of connective tissues. This disruption underlies musculocontractural Ehlers-Danlos syndrome, a rare inherited condition characterised by joint contractures, skin hyperextensibility, and skeletal abnormalities. Understanding DSE function is important for diagnosing and managing this condition.
What the gene does
Dermatan sulfate epimerase catalyses the epimerisation of glucuronic acid to iduronic acid within the growing chains of dermatan sulfate. This chemical modification is essential for the final structure and function of dermatan sulfate proteoglycans. These proteoglycans are incorporated into the extracellular matrix, where they interact with collagen fibres and other structural proteins to provide tensile strength and elasticity to connective tissues.
The enzyme operates within the Golgi apparatus, the cellular compartment where complex carbohydrates are assembled and modified before secretion. By altering the ratio of iduronic to glucuronic acid residues, DSE influences the biochemical properties of dermatan sulfate, including its ability to bind growth factors and regulate tissue hydration. Loss of DSE activity results in abnormal glycosaminoglycan composition, which in turn affects the mechanical resilience of tissues subjected to repeated stress, such as joints and skin.
Video: Genetics 101
Chromosome location
DSE is located at chromosomal position 6q22.1 on the long arm of chromosome 6. The gene comprises multiple exons that encode a protein of 958 amino acids. This genomic region contains other genes involved in skeletal and connective tissue development, though DSE functions independently in dermatan sulfate biosynthesis.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The DSE enzyme is predicted to function as a single polypeptide chain that localises to the Golgi membrane, where it accesses nascent glycosaminoglycan chains during proteoglycan synthesis. Structural studies of related epimerases suggest that the protein likely contains catalytic regions responsible for recognising the carbohydrate substrate and performing the epimerisation reaction.
Key variants
Pathogenic variants in DSE are inherited in an autosomal recessive pattern, meaning that affected individuals carry two altered copies of the gene. These variants typically result in reduced or absent enzyme activity, leading to deficient dermatan sulfate production. The variant landscape includes missense changes that disrupt catalytic function and nonsense or frameshift variants that produce truncated, non-functional proteins.
Sample of pathogenic variants
7 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.387del | p.Asp128_Tyr129insTer | Pathogenic | ★☆☆☆ | Inborn genetic diseases |
c.406C>T | p.Gln136Ter | Pathogenic | ★☆☆☆ | Ehlers-Danlos syndrome, musculocontractural type 2 |
c.480del | p.Ala161fs | Pathogenic | ★☆☆☆ | Ehlers-Danlos syndrome, musculocontractural type 2 |
c.811del | p.Gln271fs | Pathogenic | ★☆☆☆ | Ehlers-Danlos syndrome, musculocontractural type 2 |
c.874C>T | p.Gln292Ter | Pathogenic | ★☆☆☆ | Ehlers-Danlos syndrome, musculocontractural type 2 |
c.799A>G | p.Arg267Gly | Pathogenic | - | Ehlers-Danlos syndrome, musculocontractural type 2 |
c.803C>T | p.Ser268Leu | Pathogenic | - | Ehlers-Danlos syndrome, musculocontractural type 2 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Biallelic pathogenic variants in DSE cause Ehlers-Danlos syndrome (musculocontractural), a connective tissue disorder characterised by congenital joint contractures, craniofacial features, skin changes, and skeletal abnormalities. Affected individuals often present in infancy with talipes equinovarus (clubfoot), multiple joint contractures, and characteristic facial features. The severity and progression of symptoms can vary, but the condition generally involves progressive joint and skin manifestations that require multidisciplinary clinical management.
Inheritance pattern
Conditions caused by pathogenic DSE variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
DSE is included on NHS Genomic Medicine Service panels for Ehlers-Danlos syndrome with a likely monogenic cause (green gene, R101 pathway) and foetal anomalies (green gene, R21 pathway). Green classification indicates strong evidence linking DSE variants to these clinical presentations, supporting the use of DSE testing in diagnostic pathways for patients with compatible clinical features. These panel memberships reflect the gene's recognised role in prenatal and postnatal diagnosis of musculocontractural Ehlers-Danlos syndrome.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the inheritance pattern for DSE-related conditions?
DSE-related Ehlers-Danlos syndrome follows an autosomal recessive inheritance pattern. This means an affected individual has inherited a pathogenic variant from both parents, each of whom typically carries one altered copy without showing symptoms.
How does DSE enzyme deficiency affect connective tissue?
Loss of DSE activity reduces the production of properly modified dermatan sulfate, a key component of the extracellular matrix. This alteration weakens the structural integrity of connective tissues, leading to joint contractures, skin hyperextensibility, and skeletal abnormalities characteristic of musculocontractural Ehlers-Danlos syndrome.
Is genetic testing for DSE available through the NHS?
Yes, DSE is included on NHS Genomic Medicine Service panels for Ehlers-Danlos syndrome and foetal anomalies. Testing is typically arranged through clinical genetics services when a patient's features suggest musculocontractural Ehlers-Danlos syndrome or related presentations identified on prenatal imaging.