Categories: Integument (skin) phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 606408 (trait) , 600985 (gene)

Links to MONDO diseases:

• MONDO:0011670: Ehlers-Danlos syndrome due to tenascin-X deficiency

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: classic-like Ehlers-Danlos syndrome (clEDS), TNXB-related; Ehlers-Danlos syndrome, classic-like, 1

Species-specific symbol: clEDS, EDS

Species-specific description: This phene has been renamed from "Ehlers-Danlos syndrome, classic-like, 1" to "classic-like Ehlers-Danlos syndrome (clEDS), TNXB-related" in OMIA on the basis of the review on human Ehlers-Danlos syndromes by Malfait et al. (2020) [2/6/2022].

Inheritance: As reported by Bauer et al. (2019): "Each variant allele was transmitted from one of the case’s parents, consistent with compound heterozygosity."

Molecular basis: Bauer et al. (2019) reported an affected mixed-breed dog that is a compound heterozygote for two potentially causal recessive TNXB variants: c.2012G>A; p.(Ser671Asn) and c.2900G>A; p.(Gly967Asp). The authors state “Given that this is a single case investigation and that we have no functional confirmation of a tenascin XB deficiency, this result must be considered preliminary and should be interpreted with caution.”

Clinical features: Bauer et al. (2019): "The dog was referred because of fragile skin that teared or bruised easily even from minor injuries, leading to severe wounds that healed poorly. According to the owner, the skin fragility had been present since the dog was a puppy. At the time of examination, the dog was 21 months old and appeared in a good general health condition. Neither wounds nor scars were present, but the skin was hyperextensible".

Prevalence: As reported by Bauer et al. (2019): "Although one of the variant alleles, XM_003431680.3:c.2012G>A, p.(Ser671Asn), was private to the family of the affected dog and absent from whole-genome sequencing data of 599 control dogs, the second variant allele, XM_003431680.3:c.2900G>A, p.(Gly967Asp), is present at a low frequency in the Chihuahua and Poodle population." Pathogenicity of both variants is questionable.

Breed: Mixed breed (dog).

Associated gene: