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.

摘要：MYH9相关疾病（MYH9-related disease）是一种由MYH9基因突变引发的常染色体显性遗传病（autosomal dominant disorder），该基因编码22号染色体q12区域（chromosome 22q12）的非肌肌球蛋白重链IIA（non-muscle myosin heavy chain IIA）。该病以先天性大血小板减少症（congenital macrothrombocytopenia）、出血倾向（bleeding tendency）、听力损失（hearing loss）及白内障（cataracts）为主要临床特征。约30%的MYH9相关疾病患者可并发肾病（nephropathy），本次报告的病例为1例携带MYH9基因外显子1（exon 1）新发错义突变（de novo missense mutation）[c.287C>T；p.Ser(TCG)96(TTG)Leu]的男性携带者。该患者具备该病的全部表型表现，唯独未出现白内障。其肾脏损害表现为镜下血尿（microhematuria）、肾病范围蛋白尿（nephrotic-range proteinuria）（最高达7.5g/24h）以及肾功能快速减退，五年内肾小球滤过率（glomerular filtration rate）年均下降20mL/min/1.73m²。临床予肾素-血管紧张素系统阻断治疗，这是目前推荐的唯一可延缓该肾病进展的治疗方案。尽管MYH9相关疾病是肾小球病及终末期肾病（end-stage renal disease）的罕见病因，但提升对罕见遗传性肾脏疾病的认知水平，对确保罕见病（orphan disease）患者获得精准诊断与规范管理至关重要。