The following is a summary of “A Novel Variant of DNM1L Expanding the Clinical Phenotypic Spectrum: A Case Report and Literature Review,” published in the February 2024 issue of Pediatrics by Zhang et al.
Mitochondrial diseases exhibit considerable clinical and genetic heterogeneity. The dynamin 1-like gene (DNM1L) encodes dynamin-related protein 1 (DRP1), a key player in mitochondrial and peroxisomal fission. DNM1L variants can disrupt mitochondrial fission, contributing to disease pathology. Researchers present a unique clinical phenotype associated with a novel DNM1L variant and conduct a comprehensive literature review. A 5-year-old girl presented with paroxysmal hemiplegia, astigmatism, and strabismus, responding well to levocarnitine and coenzyme Q10 supplementation. Trio whole-exome sequencing (trio-WES) and mtDNA sequencing identified a de novo heterozygous nonsense variant (c.2161C>T, p.Gln721Ter) in exon 20 of the DNM1L gene, deemed pathogenic per ACMG guidelines.
Notably, the patient displayed hemiparesis, an unreported clinical manifestation potentially broadening the phenotypic spectrum of DNM1L-related diseases. Their findings underscore the importance of next-generation sequencing in early diagnosis and advocate for further clinical and genetic analyses to enhance understanding and management of DNM1L-related disorders.
Source: bmcpediatr.biomedcentral.com/articles/10.1186/s12887-023-04442-y