Re-evaluating the MYH9 p.I1816V variant in a patient with atypical clinical presentation.

Area of Science:

• Genetics
• Nephrology
• Hematology

Background:

• MYH9-related disease (MYH9-RD) is an autosomal dominant disorder.
• Characterized by macrothrombocytopenia, leukocyte inclusions, hearing loss, and nephropathy.
• The non-muscle myosin heavy chain IIA (NMMHC-IIA) is encoded by the MYH9 gene.

Purpose of the Study:

• To describe a case of a 16-year-old boy with kidney disease and a rare MYH9 variant.
• To investigate the clinical presentation and genetic findings in relation to MYH9-RD.
• To highlight diagnostic challenges posed by rare genetic variants.

Main Methods:

• Clinical case presentation.
• Kidney biopsy analysis.
• Genetic testing for MYH9 variants.
• Assessment of NMMHC-IIA expression in neutrophils and podocytes.

Main Results:

• The patient presented with persistent proteinuria and biopsy-proven membranous nephropathy with focal segmental sclerosis.
• Genetic testing revealed a rare MYH9 variant (p.I1816V), previously linked to Epstein syndrome.
• The patient exhibited normal platelet counts, absence of leukocyte inclusions, and normal NMMHC-IIA expression.
• The p.I1816V variant is predicted to be benign by in silico tools and is more prevalent in East Asian populations.

Conclusions:

• This case underscores the difficulties in interpreting rare MYH9 variants, especially when clinical features do not align with typical MYH9-RD.
• The findings emphasize the need for careful evaluation of genetic variants in conjunction with clinical presentation, particularly with advances in next-generation sequencing.
• Further research is needed to fully understand the pathogenicity and clinical significance of rare MYH9 variants.