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Editorial
. 2024 Aug 8;64(2):2401026.
doi: 10.1183/13993003.01026-2024. Print 2024 Aug.

Not all are the same: the power of registries in defining genotype-phenotype relationships in primary ciliary dyskinesia

Amjad Horani  1   2 , Pleasantine Mill  3   2
Affiliations
Editorial

Not all are the same: the power of registries in defining genotype-phenotype relationships in primary ciliary dyskinesia

Amjad Horani et al. Eur Respir J. .
No abstract available

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Conflict of interest statement

Conflict of interest: A. Horani reports support for the present study from National institute of health (K08HL150223). P. Mill reports support for the present study from UKRI Medical Research Council (MC_PC_21044, MR_Y015002_1) and European Research Council (ERC) (grant number 866355), payment or honoraria for lectures, presentations, manuscript writing or educational events from Pfizer, and leadership roles within Ciliopathy Alliance (scientific advisory board member) and PCD Research (scientific advisory panel member).

Figures

Figure 1
Figure 1. Revealing genotype-phenotype relationships in PCD.
(A) Schematic of motile cilia axoneme cross-section representing ultrastructure required for motility (healthy donor) compared to groups based on structure affected in patients with PCD. 52 PCD genes are listed in italics, with superscript (N) representing near normal ultrastructure. Outer dynein arm (red); inner dynein arm (orange); nexin dynein regulatory complex (green); radial spokes (blue) and central pair apparatus (dark grey). (B) Study overview with number of patients with PCD included from the ERN-LUNG International PCD registry, who carry pathogenic variants in 46 genes. (C) Analysis of large cohorts reveal genotype-phenotype relationships at a gene-level, such as for lung function (FEV1) both as individual data points and longitudinally. Patients with variants in CCDC39, CCDC40 and CCNO have significantly worse lung function (red dial, left) and decline faster than patients with variants in DNAH11 or ODAD1 (green dial, right). (D) In contrast, situs defects are not observed in patients with PCD who have pathogenic variants affecting genes required for motile multiciliogenesis, radial spokes, central apparatus or nexin dynein regulatory complex (blue box, left), in contrast to those affecting formation or function of dynein arms which do show situs inversus totalis or heterotaxy (purple box, right). Elements of figure panels created with BioRender.
See this image and copyright information in PMC

Comment on

  • Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations.
    Raidt J, Riepenhausen S, Pennekamp P, Olbrich H, Amirav I, Athanazio RA, Aviram M, Balinotti JE, Bar-On O, Bode SFN, Boon M, Borrelli M, Carr SB, Crowley S, Dehlink E, Diepenhorst S, Durdik P, Dworniczak B, Emiralioğlu N, Erdem E, Fonnesu R, Gracci S, Große-Onnebrink J, Gwozdziewicz K, Haarman EG, Hansen CR, Hogg C, Holgersen MG, Kerem E, Körner RW, Kötz K, Kouis P, Loebinger MR, Lorent N, Lucas JS, Maj D, Mall MA, Marthin JK, Martinu V, Mazurek H, Mitchison HM, Nöthe-Menchen T, Özçelik U, Pifferi M, Pogorzelski A, Ringshausen FC, Roehmel JF, Rovira-Amigo S, Rumman N, Schlegtendal A, Shoemark A, Sperstad Kennelly S, Staar BO, Sutharsan S, Thomas S, Ullmann N, Varghese J, von Hardenberg S, Walker WT, Wetzke M, Witt M, Yiallouros P, Zschocke A, Ziętkiewicz E, Nielsen KG, Omran H. Raidt J, et al. Eur Respir J. 2024 Aug 8;64(2):2301769. doi: 10.1183/13993003.01769-2023. Print 2024 Aug. Eur Respir J. 2024. PMID: 38871375 Free PMC article.

References

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