Genotype-phenotype Correlation of the p.R1165C Mutation in the MYH9 Disorder: Report of a Japanese Pedigree

MYH9 disorder is a rare autosomal dominant disease characterized by congenital thrombocytopenia with giant platelets and leukocyte inclusion bodies and is often associated with Alport-like symptoms, such as glomerulonephritis, sensorineural hearing loss, and cataracts. We report a Japanese pedigree wherein the MYH9 p.R1165C mutation was present in over 4 generations. Three individuals were misdiagnosed as Bernard-Soulier syndrome carriers. Among the 12 patients with abnormal hematological features, the proband's mother, aunt, and grandaunt presented with sensorineural hearing impairment, and the mother presented with presenile cataract, and nephritis. This case report confirms the previously established genotype-phenotype correlations of the MYH9 disorder that p.R1165C is associated with variable expression of nonhematological manifestations. Careful detection of leukocyte inclusion bodies in peripheral blood smears is necessary to prevent misdiagnosis.