L WONG 1,2, L HUANG 1,2, M NEDELJKOVIC 2,3, A IRISH 4, L MCMAHON 1,2
1Department of Renal Medicine, Eastern Health, Box Hill 3128, Australia, 2Eastern Health Clinical School, Monash University, Box Hill 3128, Australia, 3Department of Haematology, Eastern Health, Box Hill 3128, Australia, 4Department of Nephrology, Fiona Stanley Hospital, Murdoch 6150, Australia
Background: MYH9-related disease (MYH9RD) is a rare autosomal dominant disorder caused by mutations in MYH9, which encodes for the heavy chain of non-muscle myosin IIA, a cytoskeletal contractile protein that is expressed in all haematopoietic cells, kidney, eye and ear. The cardinal manifestations of MYH9RD are macrothrombocytopenia and neutrophilic inclusion bodies.
Case Report: We report a family pedigree with at least 2 affected members, carrying a novel missense mutation in the MYH9 gene. The proband, a 61-year-old Caucasian man, was diagnosed with chronic kidney disease (CKD) and proteinuria 30 years prior to commencing dialysis, but never had a kidney biopsy performed. He was diagnosed with bilateral sensorineural hearing loss (SNHL) and mild tri-lineage cytopenia at age 50. He had no clinically-evident bleeding tendency. Bone marrow aspirate and trephine biopsy as well as peripheral blood smears were unremarkable. A recent Wright-Giemsa stain of peripheral blood showed giant platelets and neutrophilic Döhle-like inclusion bodies. The proband’s son was also diagnosed with nephrotic-range proteinuria, CKD and bilateral SNHL, without an abnormal blood film at age 23. Initial kidney biopsy showed focal segmental glomerulosclerosis (FSGS) and thin basement membrane, with progressive focal sclerosis and thinning of the basement membrane in 50% of glomeruli at repeat biopsy age 34. Following a negative targeted gene panel testing including COL4A3, COL4A4 and COL4A5, a wider genome analysis was performed and both were heterozygous for a novel missense mutation (1271G>A) in exon 12 of MYH9, resulting in substitution of arginine for glutamine at amino acid position 424.
Conclusions: FSGS with thin glomerular basement membrane, deafness, and a supportive family history requires additional genetic testing for rare hereditary kidney diseases other than Alport syndrome.
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