Ehlers-Danlos syndrome with absence of dermatan sulfate proteoglycan

Phene ID

3381

Name

Ehlers-Danlos syndrome with absence of dermatan sulfate proteoglycan

Phene Name

This bovine "variant form of Ehlers-Danlos syndrome" reported by Tajima et al. 1999 does not correspond to any of the recognized human Ehlers-Danlos syndromes summarized in the review by Malfait et al. 2020.

OMIA ID

1716

Species ID

9913

Characterised

No

Characterised Year

N/A

Tajima et al. (1999) reported a Holstein calf with clinical features very similar to the human disorder that is now called Ehlers-Danlos Syndrome, Spondylodysplastic Type, 1; EDSSPD1 (OMIM 130070). Noting that this human disorder had been attributed by Quentin et al. (1990) to a deficiency of dermatan sulfate proteoglycan, Tajima et al. (1999) sequenced the most likely candidate region of what they thought to be (see below) the homologous bovine gene encoding the deficient peptide, in the affected calf and in three normal calves. This peptide is now called epiphycan and its gene is EPYC. However, Quentin et al. (1990) clearly showed that the peptide deficiency “is the consequence of a deficiency in galactosyltransferase I (xylosylprotein 4-,B-galactosyltransferase; EC 2.4.1.133),” which is a key enzyme in the creation of functional dermatan sulfate proteoglycan. This enzyme is encoded by a gene known as B4GALT7, which is now listed as the gene which, when mutated, gives rise to the human form (mentioned above) of the bovine disorder described by Tajima et al. (1999). Review of the published information and BLAST analysis conducted in September 2024 suggests that the variant reported by Tajima et al. (1999) is not located in the EPYC gene for dermatan sulfate proteoglycan, but in the ACAN gene, encoding bovine chondroitin sulfate proteoglycan core protein 1, also called aggrecan. This conclusion is supported by Tajima et al. (1999) reporting that their primers were obtained from sequence information in a paper concerned solely with “bovine cartilage proteoglycan”. Variants in ACAN are known to cause skeletal abnormalities in multiple species, but are not known to be associated with delayed wound healing, skin fragility, and soft and hyper-extensible skin. For all the reasons summarised above, the published variant (previously listed as omia.variant:191; EPYC;  ARS-UCD1.2: Chr5:g.20856381C>A; c.258G>T; p.(S87N); rs5334475097), that was present in a single affected Holstein calf is therefore unlikely to be causal and is no longer listed in the OMIA variant table.