LRRC56 – Primary Ciliary Dyskinesia

Biallelic LRRC56 variants have been reported in two unrelated cases of autosomal recessive Primary Ciliary Dyskinesia. In a consanguineous Arab family, a seven-year-old boy presented with situs inversus totalis, chronic sinusitis, recurrent respiratory infections, infertility, and failure to thrive; next-generation sequencing identified him homozygous for c.494T>C (p.Leu165Pro) (PMID:36176820). A prenatal study using CNV-seq and WES revealed a second LRRC56 variant (c.755del) in a fetus with situs inversus (PMID:39875822). Family history included two paternal uncles with compatible PCD features, consistent with autosomal recessive inheritance and segregation (two affected relatives).

In silico protein structure and function predictions support a loss-of-function mechanism for both the missense and deletion alleles; no cellular or animal model validation has yet been reported. Additional functional assays and extended pedigree genotyping are needed to substantiate pathogenicity fully.

Key take-home: Biallelic LRRC56 variants are emerging as a genetic cause of autosomal recessive PCD, but further segregation and experimental validation are required for definitive clinical utility.

References

• Cureus • 2022 • Primary Ciliary Dyskinesia: Phenotype Resulting From a Novel Variant of LRRC56 Gene. PMID:36176820
• BMC Genomics • 2025 • Application of copy number variation sequencing combined with whole exome sequencing in prenatal left-right asymmetry disorders. PMID:39875822

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