Ehlers-Danlos syndrome(EDS) is a hereditary connective tissue disorder characterized by skin hyperextensibility, joint hypermobility, and vascular fragility. The EDS is divided into 13 types according to the 2017 International Classification of the Ehlers-Danlos syndrome. Classical EDS (cEDS) is characterized by joint hypermobility, skin hyperextensibility, and atrophic scar. In more than 90% of parents with cEDS, autosomal dominant collagen V mutations have been identified, and approximately half are null- allele mutations resulting in COL5A1 haploinsufficiency. Collagen V is quantitatively minor, and expressed in dermis, tendons, ligaments, bones, blood vessels, and cornea. An 18-year-old Japanese female visited our hospital with recurrent dislocation of both shoulders, increased range of joint motion, and skin hyperextensibility. For molecular diagnosis, target exome sequencing was performed by MLPA (Multiplex Ligation- dependent Probe Amplification). Evaluation of potential pathogenicity of detected missense mutation was conducted using PolyPhen-2, Mutation testing. Ultimately, cEDS is diagnosed by identifying a heterozygous mutation in COL5A1 which has not been reported previously. A novel variant of c. 1388C>A (p. P463Q) was detected in the patient and her father who showed a similar clinical manifestation with a stretchable skin.

A novel COL5A1 mutation in a classic type of Ehlers-Danlos syndrome