Rare Diseases Symptoms Automatic Extraction

A COL7A1 mutation causes dystrophic epidermolysis bullosa in Rotes Höhenvieh cattle.

[dystrophic epidermolysis bullosa]

We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010. The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle. All affected calves were euthanized on humane grounds due to the severity, extent and progression of the skin and oral lesions. Examination of skin samples under light microscopy revealed detachment of the epidermis from the dermis at the level of the dermo epidermal junction, leading to the diagnosis of a subepidermal bullous dermatosis such as epidermolysis bullosa. The pedigree was consistent with monogenic autosomal recessive inheritance. We localized the causative mutation to an 18 Mb interval on chromosome 22 by homozygosity mapping. The COL7A1 gene encoding collagen type VII alpha 1 is located within this interval and COL7A1 mutations have been shown to cause inherited dystrophic epidermolysis bullosa (DEB) in humans. A SNP in the bovine COL7A1 exon 49 (c.4756C>T) was perfectly associated with the observed disease. The homozygous mutant T/T genotype was exclusively present in affected calves and their parents were heterozygous C/T confirming the assumed recessive mode of inheritance. All known cases and genotyped carriers were related to a single cow, which is supposed to be the founder animal. The mutant T allele was absent in 63 animals from 24 cattle breeds. The identified mutation causes a premature stop codon which leads to a truncated protein representing a complete loss of COL7A1 function (p.R1586*). We thus have identified a candidate causative mutation for this genetic disease using only three cases to unravel its molecular basis. Selection against this mutation can now be used to eliminate the mutant allele from the Rotes Höhenvieh breed.

Diseases presenting "premature stop codon" symptom

  • aromatase deficiency
  • cadasil
  • classical phenylketonuria
  • cohen syndrome
  • cystinuria
  • dystrophic epidermolysis bullosa
  • erythropoietic protoporphyria
  • familial hypocalciuric hypercalcemia
  • junctional epidermolysis bullosa
  • kindler syndrome
  • lamellar ichthyosis
  • omenn syndrome
  • triple a syndrome
  • x-linked adrenoleukodystrophy

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