Macrothrombocytopenia, renal dysfunction and nephrotic syndrome in a young male patient: a case report of MYH9-related disease

Abstract

MYH9-related disease is an autosomal dominant disorder caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA on chromosome 22q12. It is characterized by congenital macrothrombocytopenia, bleeding tendency, hearing loss, and cataracts. Nephropathy occurs in approximately 30% of MYH9-related disease in a male patient carrier of a de novo missense mutation in exon 1 of the MYH9 gene [c.287C > T; p.Ser(TCG)96(TTG)Leu]. He presented all phenotypic manifestations of the disease, but cataracts. Renal alterations were microhematuria, nephrotic-range proteinuria (up to 7.5 g/24h), and rapid loss of renal function. The decline per year of the glomerular filtration rate was 20 mL/min/1.73m2 for five years. Blockade of the renin-angiotensin system, the only recommended therapy for slowing the progression of this nephropathy, was prescribed. Although MYH9-related disease is a rare cause of glomerulopathy and end-stage renal disease, awareness of rare genetic kidney disorders is essential to ensure accurate diagnosis and proper management of orphan disease patients.

The potential impact of MYH9 gene (rs3752462) and ELMO1 (rs741301) variants on the risk of Nephrotic syndrome incidence

“…Tavira et al [25]found that both CT+TT genotypes were risk factors for developing CKD in the Spanish population similar to our results. Our nding matches with Sevignani et al [23]who reported that there was a mutation of the MYH9 gene (c >T)in patients with nephropathyand the diagnosis of patients with nephropathy associated with mutations in MYH9 [26]. Zhao et al [27]noted that MYH9 rs3752462 is signi cantly associated with an increased risk of diabetic kidney disease (DKD) in Chinese Han individuals.…”

“…The MYH9 gene contains 1960 amino acids. The MYH9 gene is expressed in different tissues, especially podocytes and mesangial cells [23]. MYH9 is more localized in the nucleus and cytoplasm of neutrophil granulocytes as shown in Figure 1.…”

Rare inherited kidney diseases: an evolving field in Nephrology

“…The patient had nephrotic proteinuria and a progressive loss of renal function, with an annual decline in estimated glomerular filtration rate of 18 mL/ min/1.73m 2 /year in the last 5 years. Unfortunately, he has not adhered to the use of ACE inhibitor at the onset of the disease, which may have blurred the potential benefit of renin-angiotensin-system blockade in the course of the disease 44 .…”