A de novo heterozygous CFAP43 truncating variant identified in a patient with combined dystonia

A de novo heterozygous CFAP43 truncating variant identified in a patient with combined dystonia Combined dystonia is a neurological movement disorder with significant clinical and genetic heterogeneity.Affected individuals present with abnormal postures and repetitive movements, often accompanied by multisystem features such as ataxia and cognitive impairment.The underlying etiology remains unknown in many cases 1 .To investigate candidate genetic contributors to unresolved dystonia, we performed wholeexome sequencing in 150 Chinese patients with dystonia who were consecutively recruited from the Department of Neurology, Xiangya Hospital, Central South University.Detailed recruitment criteria, clinical evaluation procedures, and genetic analysis methods are provided in the Supplementary Materials.During variant prioritization, established dystonia-associated genes were systematically evaluated.No pathogenic or likely pathogenic variant in known dystonia-associated genes was detected in the proband described here.We therefore prioritized a rare de novo heterozygous truncating variant in the Cilia and Flagella Associated Protein 43 (CFAP43) gene for further interpretation and preliminary functional assessment.The CFAP43 gene encodes an axonemal protein associated with cilia and flagella, with a core function in assembling and stabilizing axonemal dynein arms.Pathogenic CFAP43 mutations have been reported as a genetic cause of male infertility 2 .Notably, public transcriptomic resources indicate that CFAP43 transcripts are detectable in human brain tissues, particularly in the choroid plexus 3 .A previous whole-exome sequencing study identified a loss-of-function variant in CFAP43 that segregated with normal-pressure hydrocephalus in a Japanese family and showed that Cfap43-deficient J o u r n a l P r e -p r