Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility

PROPOSE: We here present a female case with primary ciliary dyskinesia (PCD) and infertility. In this report, we also present the evaluation of the patient family, including her twin sister, also with PCD and infertility. METHODS: Confirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole-exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization. RESULTS: We identified a homozygous nonsense variant in the DRC1 gene (NM 145038.5:c.352C>T (p.Gln118Ter)) in the female patient with PCD and infertility that fit the model of autosomal recessive genetic transmission. This variant eventually results in a dyskinetic ciliary beat with a lower frequency and a partial lack of both dynein arms as revealed by TEM analysis. Moreover, this variant implies a decrease in the expression of DRC1 mRNA and protein. Additionally, expression analysis suggested that DRC1 may interact with other DRC elements. CONCLUSIONS: Our findings suggest that the DRC1 null variant leads to PCD associated with infertility, likely caused by defects in axoneme from Fallopian tube cilia. Overall, our outcomes contribute to a better understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and they highlight the interaction of different genes in the patient phenotype, which should be investigated further because it may explain the high heterogeneity observed in PCD patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-023-02755-6.