MYO1E – Steroid‑Resistant Nephrotic Syndrome

This summary outlines the association between MYO1E and steroid‑resistant nephrotic syndrome. Multiple independent studies have implicated MYO1E variants in the pathogenesis of this condition, with evidence from both case reports and multi‑patient genetic studies supporting a strong gene‑disease relationship (PMID:31520189, PMID:21697813).

Clinical genetic investigations in consanguineous pedigrees and isolated cases have revealed homozygous or compound heterozygous changes in MYO1E following an autosomal recessive inheritance pattern. For instance, a recurrent variant, c.475G>C (p.Ala159Pro), was identified in affected individuals where segregation analysis confirmed its co‑segregation with disease in multiple affected siblings (PMID:21756023).

Segregation analyses from several family‐based studies further substantiate the pathogenicity of MYO1E alterations, with additional affected relatives corroborating the variant’s influence on the phenotype. The accumulation of such genetic evidence raises confidence in a strong gene‑disease association.

Functional assessments have provided complementary evidence that pathogenic MYO1E variants impair podocyte function. In vitro assays demonstrated disrupted protein localization, altered actin dynamics, and reduced ATPase activity in variants such as those affecting the motor domain, consistent with a deleterious impact on the glomerular filtration barrier (PMID:36316095).

While some studies have identified additional variants in other nephrotic syndrome–associated genes, the specific disruption of MYO1E function and its replication in independent cohorts strengthen its role in steroid‑resistant nephrotic syndrome. This integrated evidence from genetics and functional experiments aligns with clinical observations in affected patients.

Key take‑home: The convergence of robust genetic segregation, recurrent variant detection, and consistent functional deficits in podocyte biology support the clinical utility of MYO1E testing in diagnosing steroid‑resistant nephrotic syndrome.

References

• Molecular genetics and genomics : MGG • 2020 • Promises and pitfalls of whole‑exome sequencing exemplified by a nephrotic syndrome family PMID:31520189
• Kidney international • 2011 • Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid‑resistant nephrotic syndrome PMID:21697813
• Journal of the American Society of Nephrology : JASN • 2022 • Steroid‑Resistant Nephrotic Syndrome‑Associated MYO1E Mutations Have Differential Effects on Myosin 1e Localization, Dynamics, and Activity PMID:36316095

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