Orphanet journal of rare diseases · 2026
Estimation of the genetic susceptibility prevalence of primary ciliary dyskinesia via the gnomAD v4.1.0 database.
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Dai Rutao, Dao Ya, Zhang Xichen, Ma Yongyu, Zhu Xian, Gao Yunshan, Wu Jun, Sun Liu
Аннотация
BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder that is predominantly inherited in an autosomal recessive pattern and is caused by structural or functional ciliary abnormalities. Previous studies on the genetic susceptibility prevalence of PCD have been largely based on limited populations, and there is a lack of global estimates derived from large-scale population genetic databases. This study estimates the carrier frequency and genetic susceptibility prevalence of PCD via the latest data from the gnomAD v4.1.0 database and compares the results with those of previous studies.
METHODS: We selected genes related to PCD with "Definitive" or "Strong" associations as determined by the ClinGen Motile Ciliopathy Gene Curation Expert Panel. According to ACMG/AMP guidelines, variables were classified for pathogenicity, including loss-of-function variants (pLOFs) and pathogenic/likely pathogenic missense variants. Using the allele frequency (AF) of these variants from the Genome Aggregation Database (gnomAD) v4.1.0 (containing data from 807,162 individuals) and applying the Hardy‒Weinberg equilibrium principle, we calculated the global and population-specific genetic susceptibility prevalence and carrier frequency of PCD.
RESULTS: Among the 31 PCD-associated genes, 5252 eligible variants were included, comprising 5156 pLOF and 96 P/LP variants. The estimated global genetic susceptibility prevalence of PCD is approximately 1 in 20,103, with a corresponding overall carrier frequency of approximately 1 in 25. The Middle East region has the highest prevalence rate of 1 in 4,744, as well as the highest carrier frequency.
CONCLUSION: The estimated global genetic susceptibility prevalence of primary ciliary dyskinesia is approximately 1 in 20,103, with an overall carrier frequency of 1 in 25, indicating significant heterogeneity among ethnic populations. The global genetic susceptibility prevalence estimate is lower than the previous estimate of 1/7,554.
METHODS: We selected genes related to PCD with "Definitive" or "Strong" associations as determined by the ClinGen Motile Ciliopathy Gene Curation Expert Panel. According to ACMG/AMP guidelines, variables were classified for pathogenicity, including loss-of-function variants (pLOFs) and pathogenic/likely pathogenic missense variants. Using the allele frequency (AF) of these variants from the Genome Aggregation Database (gnomAD) v4.1.0 (containing data from 807,162 individuals) and applying the Hardy‒Weinberg equilibrium principle, we calculated the global and population-specific genetic susceptibility prevalence and carrier frequency of PCD.
RESULTS: Among the 31 PCD-associated genes, 5252 eligible variants were included, comprising 5156 pLOF and 96 P/LP variants. The estimated global genetic susceptibility prevalence of PCD is approximately 1 in 20,103, with a corresponding overall carrier frequency of approximately 1 in 25. The Middle East region has the highest prevalence rate of 1 in 4,744, as well as the highest carrier frequency.
CONCLUSION: The estimated global genetic susceptibility prevalence of primary ciliary dyskinesia is approximately 1 in 20,103, with an overall carrier frequency of 1 in 25, indicating significant heterogeneity among ethnic populations. The global genetic susceptibility prevalence estimate is lower than the previous estimate of 1/7,554.