A Novel Splice Site Variant in <i>KLHL40</i> Gene in Multiple Affected NEM8 Family Members Who Present Phenotypic Variability

Abstract

<b><i>Introduction:</i></b> Nemaline myopathy (NEM) is a heterogeneous muscle disease, which usually presents with hypotonia and muscle weakness. Biallelic pathogenic variants of <i>KLHL40</i> gene cause severe form of NEM (NEM8), which leads to a wide range of symptoms, including hypotonia, muscle weakness, joint contractures and fractures. Nemaline bodies in muscle fiber are characteristic findings of the disease. <b><i>Case Presentation:</i></b> Here, we presented three affected individuals in a family with variable phenotypes, in whom the same novel splice-site variant in <i>KLHL40</i> gene (c.1607+3A&gt;T) was detected. <b><i>Discussion:</i></b> This study expanded the spectrum of genotype and phenotype of NEM8, and emphasized that molecular genetic tests are highly valuable in diagnosis of patients with inconclusive muscle biopsy results.