Chediak-Higashi Syndrome

Gene: LYST

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.

Mutation: Substitution, LYST gene; c.(6044>G), p.(H2015R), chr.28.

Medical systems: Blood, immune, dermal

Breeds: Japanese Black (Wagyu)

Age of onset of symptoms: From birth.

Chediak-Higashi Syndrome is a genetic disease of economic importance seen in Japanese Black (Wagyu) cattle, characterized by excessive bleeding and bruising due to altered platelet function.  Also, there is impaired immune activity due to altered leukocyte functions, and a partial albinism due to a deficiency in melanosome transport.  A mutation in affected cattle was identified in the LYST gene, whose protein product is involved in intracellular lysosomal trafficking.  When the LYST gene is mutated, there is a defect in vesicle function in the cytoplasm.  Within platelets there is reduced calcium mobilization resulting in insufficient platelet aggregation and abnormal clot formation.  A survey of 102 Wagyu cattle revealed a frequency of carriers (M/N) of 8.8%.  The availability of a DNA test will enable producers to identify carrier animals and eliminate the disease and eventually the mutation from their animals.

References:

OMIA link: [0185-9913]

Abdeen A, Sonoda H, Kobayashi I, et al. (2013) A new method for rapid detection of the mutant allele for Chediak-Higashi syndrome in Japanese Black Cattle. J Vet Med Sci 75(9):1237-9.  [pm/23615171]

Shiraishi M, Ogawa H, Ikeda M, et al. (2002) Platelet dysfunction in Chediak-Higashi syndrome-affected cattle. J Vet Med Sci 64(9):751-760.  [pm/12399597]

Yamakuchi H, Agaba M, Hirano T, et al. (2000) Chediak-Higashi syndrome mutation and genetic testing in Japanese black cattle (Wagyu). Animal Genetics 31(1):13-19. [pm/10690356]

Kunieda T, Nakagiri M, Takami M, et al. (1999) Cloning of bovine LYST gene and identification of a missense mutation associated with Chediak-Higashi syndrome of cattle. Mamm Genome 10(12):1146-9. [pm/10594238]

Contributed by: Simon Larue and Camille Barr, Class of 2028, Faculty of Veterinary Medicine, University of Montreal.  (Translation, DWS)