Ichthyosis (ABCA12-related)

Gene: ABCA12

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Chianina mutation: Substitution, ABCA12 gene: c.5804A>G, p.(His1935Arg), exon39, Chr.2.

Shorthorn mutation: Substitution, ABCA12 gene: c.6776T>C, p.(Leu2259Pro, Chr.2.

Polled Herford: mutation Insertion, ABCA12 gene: c.5689_5690 insC, p.(Ser1784Ile frameshift STOP 33), exon34, Chr.2.

Medical system: Dermal

Breeds: Chianina, Shorthorn, Polled Herford

Age of onset of symptoms: From birth.

Ichthyosis is the name given to a heterologous group of skin diseases characterized by dry and scaly skin, where “ichthy-” refers to fish as in fish scales.  It can have hereditary (genetic) or acquired (environmental) causes, and is seen in numerous animal species.  In cattle, two forms of hereditary ichthyosis are reported.   Ichthyosis fetalis is a severe lethal form that involves thick skin patches with deep fissures and death occurring shortly before or after birth.  Congenital ichthyosis is less severe but still involves skin thickening, sparse hair (hypotrichosis) or lack of hair (alopecia), stiff movements and growth retardation.

Molecular studies of the ichthyosis fetalis in Chianina calves identified a mutation in the ABCA12 gene.  This gene is expressed in skin keratinocytes and codes for a protein involved in transporting lipid molecules across the cell membrane into the extracellular space.  Mutations in the ABCA12 can be the cause of some forms of ichthyosis seen in humans.  Cases of ichthyosis fetalis were also reported in Shorthorn and in Polled Herford animals and shown to be caused by independent mutations within the ABCA12 gene.  In the case of the Shorthorn mutation, a study of 130 animals revealed a carrier burden of about 7.3%.  DNA tests are available that will allow breeders to identify carrier animals such that they can eliminate the disease and eventually the mutation from their breeds by selective and judicious reproduction.

References:

OMIA link: [2238-9913]

Eager KLM, Conyers LE, Woolley SA, et al. (2020) A novel ABCA12 frameshift mutation segregates with ichthyosis fetalis in a Polled Hereford calf. Anim Genet 51:837-838.  [pm/32567073]

Woolley SA, Eager KLM, Häfliger IM, et al. (2019) An ABCA12 missense variant in a Shorthorn calf with ichthyosis fetalis. Anim Genet 50:749-752. [pm/31568573]

Charlier C, Coppieters W, Rollin F, et al. (2008) Highly effective SNP-based association mapping and management of recessive defects in livestock. Nat Genet 40:449-54.  [pm/18344998]

Testoni S, Zappulli V, Gentile A. (2006) Ichthyosis in two Chianina calves. Dtsch Tierarztl Wochenschr 113:351-4.  [pm/17009813]

With contributions by: Mathilde St-Pierre and Éloïse Paquette, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).