MCIDAS – Primary Ciliary Dyskinesia

This summary outlines the association between MCIDAS (HGNC:40050) and primary ciliary dyskinesia (MONDO_0016575), a disorder characterized by defective multiciliogenesis and consequent infertility (PMID:34569065). The evidence derives from multi‐patient studies demonstrating that bi-allelic loss-of-function mutations in MCIDAS lead to impaired formation of multiple motile cilia, a key pathological mechanism in the disease.

Genetic evidence includes the identification of homozygous frameshift mutations in MCIDAS in two unrelated consanguineous families. In one study, a pathogenic variant, c.186dup (p.Pro63SerfsTer22), was identified in a male and a female affected by primary ciliary dyskinesia, clearly establishing segregation with the phenotype (PMID:34569065). Additional evidence from a larger whole-exome sequencing (WES) study further supports the role of MCIDAS in severe cases of the disorder (PMID:38154480).

The variant c.186dup (p.Pro63SerfsTer22) represents a frameshift mutation that results in premature termination of the protein. This observation, together with the segregation data, provides compelling genetic support for MCIDAS as critical to the multiciliogenesis process in reproductive tissues.

The inheritance mode in these studies is autosomal recessive, as evidenced by the occurrence of homozygous mutations in affected individuals from families with consanguineous backgrounds. No additional affected relatives beyond the probands have been reported to contribute to the segregation count in these studies.

Functional assessments have demonstrated that loss of MCIDAS function disrupts the biogenesis and assembly of basal bodies. Immunofluorescence and transmission electron microscopy (TEM) analyses reveal the absence of MCIDAS protein and a marked reduction in basal bodies within the efferent ducts and oviducts, providing mechanistic insights that parallel the observed clinical phenotype (PMID:34569065).

Integrating the genetic and functional data, it is evident that MCIDAS mutations interfere with critical pathways required for ciliary formation. Although study sizes are small, the consistency of the phenotype across independent reports and the supportive mechanistic data lend moderate weight to the association. This evidence supports the use of genetic testing and functional assays in diagnostic decision-making for patients presenting with PCD-related infertility.

Key Take‑home sentence: The identification of the c.186dup (p.Pro63SerfsTer22) mutation in MCIDAS, coupled with robust functional data, underscores its clinical utility in diagnosing primary ciliary dyskinesia and guiding therapeutic interventions.

References

• Clinical Genetics • 2021 • Bi-allelic mutations in MCIDAS and CCNO cause human infertility associated with abnormal gamete transport PMID:34569065
• Unknown • Unknown • Whole-exome sequencing implicates MCIDAS in primary ciliary dyskinesia PMID:38154480

Evidence Based Scoring (AI generated)