Implementation of a gene panel for genetic diagnosis of primary ciliary dyskinesia

Baz-Redón, Noelia; Rovira‐Amigo, Sandra; Castillo‐Corullón, Silvia; Cols-Roig, Maria; Antolı́n, Maria; García‐Arumí, Elena; Torrent‐Vernetta, Alba; Messa, Inés de Mir; Gartner, Sílvia; Serrano, Ignacio Iglesias; Caballero‐Rabasco, María Araceli; Cruz, Oscar A.; Vizmanos-Lamotte, Gerardo; Vicente, Carlos Martín de; Martínez-Colls, María del Mar; Reula, Ana; Escribano, Amparo; Dası́, Francisco; Armengot-Carceller, Miguel; Polverino, Eva; Pieras, Esther Amengual; Amaro-Rodríguez, Rosanel; Garrido-Pontnou, Marta; Tizzano, Eduardo F.; Camats-Tarruella, Núria; Fernández‐Cancio, Mónica; Moreno‐Galdó, Antonio

doi:10.1016/j.arbr.2021.01.003

Cited by 10 publications

(9 citation statements)

References 45 publications

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“…Following the European Respiratory Society guidelines for PCD diagnosis [ 26 ] and in-house optimised protocols, we evaluated the ciliary function and structure in the proband, siblings and mother with a clinical symptoms questionnaire and PICADAR (PrImary CiliARy DyskinesiA Rule) score [ 27 ], nasal nitric oxide (nNO) screening test [ 28 ], high-speed video-microscopy analysis (HSVM) [ 29 ], immunofluorescence (IF) [ 30 ] and transmission electron microscopy (TEM) analyses, and genetics [ 31 ] ( Supplementary Materials , [ 32 , 33 , 34 , 35 , 36 , 37 ]).…”

Section: Methodsmentioning

confidence: 99%

Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel RPGR Variant and Possible Modifier Gene

Baz-Redón,

Sánchez-Bellver,

Fernández-Cancio

et al. 2024

Cells

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We report a novel RPGR missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the RPGR variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The pathogenicity of the variant on the RPGR protein was evaluated by in vitro studies transiently transfecting the mutated RPGR gene, and immunofluorescence analysis on nasal brushing samples. Whole-exome sequencing was conducted to identify potential modifier variants. In vitro studies showed that the mutated RPGR protein could not localise to the cilium and impaired cilium formation. Accordingly, RPGR was abnormally distributed in the siblings’ nasal brushing samples. In addition, a missense variant in CEP290 was identified. The concurrent RPGR variant influenced ciliary mislocalisation of the protein. We provide a comprehensive characterisation of motile cilia in this XLRP family, with only the proband presenting PCD symptoms. The variant’s pathogenicity was confirmed, although it alone does not explain the respiratory symptoms. Finally, the CEP290 gene may be a potential modifier for respiratory symptoms in patients with RPGR mutations.

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Section: Methodsmentioning

confidence: 99%

Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel RPGR Variant and Possible Modifier Gene

Baz-Redón,

Sánchez-Bellver,

Fernández-Cancio

et al. 2024

Cells

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“…Disease-causing mutations in at least 40 genes have already been reported [169]. It is characterized by structural and/or functional alteration in motile cilia, which causes a deficit in the mucociliary clearance of the respiratory secretions [170] leading to chronic respiratory infections and chronic inflammation of the airways. An inefficient inflammatory process increases the number of neutrophils, increasing ROS and RNS, as explained above [171].…”

Section: Primary Ciliary Dyskinesia and Oxidative Stressmentioning

confidence: 99%

Rare Respiratory Diseases: A Personal and a Public Health Problem

2022

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“… 7 However, its non-specific manifestations and the difficulties associated with accessing the highly sophisticated diagnostic tests and facilities often delay diagnosis and treatment. 1 8 9 These effects are compounded by the requirement for invasive procedures, including nasal or lung biopsies, and patient participation, such as in nasal nitric oxide (nNo) testing, particularly in children. 1 9 10 …”

Section: Introductionmentioning

confidence: 99%

“… 1 8 9 These effects are compounded by the requirement for invasive procedures, including nasal or lung biopsies, and patient participation, such as in nasal nitric oxide (nNo) testing, particularly in children. 1 9 10 …”

Section: Introductionmentioning

confidence: 99%

“…Recent PCD guidelines specify genetic testing as one of the essential methods for PCD diagnosis. 1 8 9 10 11 12 In fact, P variants have been identified in more than 40 PCD-related genes with a genetic diagnostic yield estimated to be 30%–70% among suspected or confirmed PCD patients. However, this yield is expected to increase as new genes related to PCD are identified.…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of Primary Ciliary Dyskinesia via Whole Exome Sequencing and Histologic Findings

Oh,

Lee,

Park

et al. 2024

Yonsei Med J

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Purpose To assess the diagnostic potential of whole-exome sequencing (WES) and elucidate the clinical and genetic characteristics of primary ciliary dyskinesia (PCD) in the Korean population. Materials and Methods Forty-seven patients clinically suspected of having PCD were enrolled at a tertiary medical center. WES was performed in all patients, and seven patients received biopsy of cilia and transmission electron microscopy (TEM). Results Overall, PCD was diagnosed in 10 (21.3%) patients: eight by WES (8/47, 17%), four by TEM. Among patients diagnosed as PCD based on TEM results, two patients showed consistent results with WES and TEM of PCD (2/4, 50%). In addition, five patients, who were not included in the final PCD diagnosis group, had variants of unknown significance in PCD-related genes (5/47, 10.6%). The most frequent pathogenic (P)/likely pathogenic (LP) variants were detected in DNAH11 (n=4, 21.1%), DRC1 (n=4, 21.1%), and DNAH5 (n=4, 21.1%). Among the detected 17 P/LP variants in PCD-related genes in this study, 8 (47.1%) were identified as novel variants. Regarding the genotype–phenotype correlation in this study, the authors experienced severe PCD cases caused by the LP/P variants in MCIDAS , DRC1 , and CCDC39 . Conclusion Through this study, we were able to confirm the value of WES as one of the diagnostic tools for PCD, which increases with TEM, rather than single gene tests. These results will prove useful to hospitals with limited access to PCD diagnostic testing but with relatively efficient in-house or outsourced access to genetic testing at a pre-symptomatic or early disease stage.

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Implementation of a gene panel for genetic diagnosis of primary ciliary dyskinesia

Cited by 10 publications

References 45 publications

Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel RPGR Variant and Possible Modifier Gene

Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel RPGR Variant and Possible Modifier Gene

Rare Respiratory Diseases: A Personal and a Public Health Problem

Diagnosis of Primary Ciliary Dyskinesia via Whole Exome Sequencing and Histologic Findings

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