A Novel Splice Site Variant in KLHL40 Gene in Multiple Affected NEM8 Family Members Who Present Phenotypic Variability
Molecular Syndromology, vol.16, no.1, pp.61-68, 2025 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 16 Issue: 1
- Publication Date: 2025
- Doi Number: 10.1159/000540325
- Journal Name: Molecular Syndromology
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.61-68
- Keywords: KLHL40, Nemaline myopathy, Splice region variant
- Dokuz Eylül University Affiliated: Yes
Abstract
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>PT) 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.