Delineation of musculocontractural Ehlers-Danlos Syndrome caused by dermatan sulfate epimerase deficiency.

Abstract

BACKGROUND:

Musculocontractural Ehlers-Danlos Syndrome (mcEDS) is a rare connective tissue disorder caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE), both of which result in defective dermatan sulfate biosynthesis. Forty-one patients with mcEDS-CHST14 and three patients with mcEDS-DSE have been described in the literature.

METHODS:

Clinical, molecular, and glycobiological findings in three additional patients with mcEDS-DSE were investigated.

RESULTS:

Three patients from two families shared craniofacial characteristics (hypertelorism, blue sclera, midfacial hypoplasia), skeletal features (pectus and spinal deformities, characteristic finger shapes, progressive talipes deformities), skin features (fine or acrogeria-like palmar creases), and ocular refractive errors. Homozygous pathogenic variants in DSE were found: c.960T>A/p.Tyr320* in patient 1 and c.996dupT/p.Val333Cysfs*4 in patients 2 and 3. No dermatan sulfate was detected in the urine sample from patient 1, suggesting a complete depletion of DS.

CONCLUSION:

McEDS-DSE is a congenital multisystem disorder with progressive symptoms involving craniofacial, skeletal, cutaneous, and cardiovascular systems, similar to the symptoms of mcEDS-CHST14. However, the burden of symptoms seems lower in patients with mcEDS-DSE.

• Authors: Charlotte K Lautrup, Keng W Teik, Ai Unzaki, Shuji Mizumoto, Delfien Syx, Heng H Sin, Irene K Nielsen, Sara Markholt, Shuhei Yamada, Fransiska Malfait, Naomichi Matsumoto, Noriko Miyake, Tomoki Kosho
• Journal: Molecular genetics & genomic medicine (Mol Genet Genomic Med) Vol. 8 Issue 5 Pg. e1197 (05 2020) ISSN: 2324-9269 [Electronic] United States
• PMID: 32130795 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Chemical References

• Dermatan Sulfate
• Chondroitin Sulfates
• Sulfotransferases
• dermatan-4-sulfotransferase-1

Topics

• Adolescent
• Chondroitin Sulfates (urine)
• Dermatan Sulfate (urine)
• Ehlers-Danlos Syndrome (genetics, pathology, urine)
• Female
• Humans
• Loss of Function Mutation
• Male
• Phenotype
• Sulfotransferases (genetics)
• Young Adult