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

INTRODUCTION: Nemaline myopathy (NEM) is a heterogeneous muscle disease, which usually presents with hypotonia and muscle weakness. Biallelic pathogenic variants of KLHL40 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. CASE PRESENTATION: Here, we presented three affected individuals in a family with variable phenotypes, in whom the same novel splice-site variant in KLHL40 gene (c.1607+3A>T) was detected. DISCUSSION: 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.