Genetic basis of CLAD III in German Shepherds - is caused by a recessive mutation in the FERMT3 gene (also known as KINDLIN-3), which encodes a protein critical for white blood cell and platelet activation. The specific mutation is a 12 base pair insertion (c.1349_1350insAAGACGGCTGCC) in FERMT3, disrupting normal protein function. This gene mutation hinders proper activation of leukocytes (white blood cells) and platelets needed for immune response and blood clotting. The condition follows an autosomal recessive inheritance pattern, meaning affected dogs have two copies of the mutation; carriers have one copy and are asymptomatic but can pass the trait on.
Pathophysiology - The defective Kindlin-3 protein results in impaired activation of integrins on leukocytes and platelets. This leads to failure of leukocytes to properly adhere and migrate to infection sites, causing severe recurrent infections. Platelet dysfunction causes bleeding tendencies with poor blood clotting. The immune deficiency and bleeding diathesis together cause a complex clinical picture affecting overall health.
Complications - Affected dogs typically present as puppies or young adults with: Recurrent severe skin infections (pyoderma), Lameness due to joint or bone infections (osteomyelitis), Gingivitis and bleeding gums, Poor wound healing and increased bleeding following trauma or surgery. The disease is chronic and often life-shortening despite supportive care. Some affected dogs can survive for years but require careful management.
Why This Matters to Breeders and Vets - Genetic testing for the FERMT3 mutation enables breeders to identify carriers and avoid carrier-to-carrier matings, preventing affected puppies. Veterinarians benefit from awareness to diagnose CLAD III, guide appropriate care, and avoid invasive procedures that might provoke bleeding complications. Early genetic identification supports better health management and breeding decisions in German Shepherd populations.
Summary - Canine Leukocyte Adhesion Deficiency Type III (CLAD III) in German Shepherd Dogs is a serious autosomal recessive disorder caused by a FERMT3 gene mutation that leads to defective leukocyte and platelet activation. Clinically, affected dogs have recurrent infections and bleeding tendencies, often presenting in puppyhood or young adulthood. Genetic testing facilitates diagnosis, carrier detection, and informed breeding strategies to improve breed health and minimize disease spread.