In other species: dog , domestic cat , sheep , rabbit , American mink

Categories: Integument (skin) phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 120150 (gene) , 130000 (trait) , 130010 (trait) , 130020 (trait) , 130050 (trait) , 130060 (trait) , 130070 (trait) , 130080 (trait) , 130090 (trait) , 147900 (trait) , 225310 (trait) , 225320 (trait) , 225400 (trait) , 225410 (trait) , 229200 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: Also known as cutaneous asthenia (CA) or hyperelastosis cutis (HC). Some animals are born with easily extendible and very fragile skin. Severe lacerations result from the slightest scratch. The basic cause of these severe clinical signs is the presence of abnormal collagen in the skin. There are several genes encoding peptides that form procollagen molecules. There are also several genes encoding enzymes that remove excess amino acids from each end of the procollagen molecules, creating mature collagen. Mutations in any of these genes can give rise to Ehlers-Danlos syndrome (see gene-specific entries in OMIA). In general, mutations in collagen structural genes result in dominant forms of the disorder, because heterozygotes produce 50 per cent abnormal collagen molecules. In contrast, mutations in the genes for the enzymes that "process" procollagen generally result in recessive forms of the disorder, because the 50 per cent of normal enzyme activity that occurs in heterozygotes is sufficient to "process" all procollagen molecules. In humans, a detailed classification of the different types of Ehlers-Danlos syndrome has been made, corresponding to mutations in the different genes involved. In animals, most occurrences of the disorder have to be lumped together because the detailed studies necessary for classification have not yet been conducted.

Species-specific name: Hereditary equine regional dermal asthenia; hyperelastosis cutis

Species-specific symbol: HERDA

History: As noted by Tyron et al. (2007), their study was "the first whole-genome scan used to identify a novel disease gene in the horse".

Inheritance: Tryon et al. (2005) provided convincing evidence of autosomal recessive inheritance in Quarter horses.

Mapping: By conducting a genome scan on 38 affected and 44 unrelated normal horses, each genotyped with 98 autosomal microsatellites, Tryon et al. (2007) used homozygosity mapping to map this disorder to a 20cM region on chromosome ECA1. Fine-mapping narrowed this region to a 2.5Mb, which (based on deductions from comparative mapping) contains around 20 genes.

Molecular basis: By sequencing the most likely of the roughly 20 positional candidate genes (see Mapping section), Tyron et al. (2007) identified a likely causative missense mutation (c.115G>A; p.39G>R) in the gene for cyclophilin B (PPIB). Ishikawa et al. (2012) confirmed the above mutation as causal, but identified it as c.115G>A; p.6G>R rather than c.115G>A; p.39G>R.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Associated gene: