Carrier status for 3 most frequentCFTR mutations in Polish PCD/KS patients: lack of association with the primary ciliary dyskinesia phenotype

Skrzypczak, Urszula; Rutkiewicz, Ewa; Pogorzelski, Andrzej; Witt, Michał; Ziętkiewicz, Ewa

doi:10.1007/bf03194662

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…At least one of the three criteria listed below had to be fulfilled to include a patient in the PCD cohort: i) typical clinical symptoms (recurrent upper respiratory tract infections, recurrent pneumonia, chronic bronchitis, bronchiectasis, sinusitis and otitis media, and reduced mucociliary clearance as shown by a negative result of a saccharine test) associated with situs inversus (85 families); (ii) typical clinical manifestation without situs inversus , but with the presence of a defect in the ciliary ultrastructure (41 families); (iii) typical clinical symptoms without situs inversus , and the absence of ciliary motility as seen in the light microscope (58 families). Cystic fibrosis was excluded on the basis of a clinical picture and an absence of most frequent CFTR mutations [35]. Parental consanguinity was reported in one family; otherwise, consanguinity was neither reported nor formally excluded.…”

Section: Methodsmentioning

confidence: 99%

Mutations in Radial Spoke Head Genes and Ultrastructural Cilia Defects in East-European Cohort of Primary Ciliary Dyskinesia Patients

et al. 2012

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Primary ciliary dyskinesia (PCD) is a rare (1/20,000), multisystem disease with a complex phenotype caused by the impaired motility of cilia/flagella, usually related to ultrastructural defects of these organelles. Mutations in genes encoding radial spoke head (RSPH) proteins, elements of the ciliary ultrastructure, have been recently described. However, the relative involvement of RSPH genes in PCD pathogenesis remained unknown, due to a small number of PCD families examined for mutations in these genes. The purpose of this study was to estimate the involvement of RSPH4A and RSPH9 in PCD pathogenesis among East Europeans (West Slavs), and to shed more light on ultrastructural ciliary defects caused by mutations in these genes. The coding sequences of RSPH4A and RSPH9 were screened in PCD patients from 184 families, using single strand conformational polymorphism analysis and sequencing. Two previously described (Q109X; R490X) and two new RSPH4A mutations (W356X; IVS3_2–5del), in/around exons 1 and 3, were identified; no mutations were found in RSPH9. We estimate that mutations in RSPH4A, but not in RSPH9, are responsible for 2–3% of cases in the East European PCD population (4% in PCD families without situs inversus; 11% in families preselected for microtubular defects). Analysis of the SNP-haplotype background provided insight into the ancestry of repetitively found mutations (Q109X; R490X; IVS3_2–5del), but further studies involving other PCD cohorts are required to elucidate whether these mutations are specific for Slavic people or spread among other European populations. Ultrastructural defects associated with the mutations were analyzed in the transmission electron microscope images; almost half of the ciliary cross-sections examined in patients with RSPH4A mutations had the microtubule transposition phenotype (9+0 and 8+1 pattern). While microtubule transposition was a prevalent ultrastructural defect in cilia from patients with RSPH4A mutations, similar defects were also observed in PCD patients with mutations in other genes.

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Section: Methodsmentioning

confidence: 99%

Mutations in Radial Spoke Head Genes and Ultrastructural Cilia Defects in East-European Cohort of Primary Ciliary Dyskinesia Patients

et al. 2012

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“…The CFTR functions as a Cl and bicarbonate (HCO 3 ) channel and is critical for the normal height of the airway surface liquid (ASL) 13. Skrzypczak et al mentioned that one of the possible candidates for the PCD modifier genes is CFTR , and the heterozygous F508del mutation was found in PCD patients 14. The observed frequency of ΔF508 carriers in the Polish PCD patients was slightly higher than expected; however, the difference was not significant.…”

Section: Discussionmentioning

confidence: 97%

Characteristics of chloride transport in nasal mucosa from patients with primary ciliary dyskinesia

Cho

Hwang

Illek³

2010

The Laryngoscope

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Objectives Primary ciliary dyskinesia (PCD) is an inherited disorder that produces lifelong difficulties with chronic airway inflammation. Little is known about the role of chronic airway inflammation on chloride ion transport properties in PCD. This study is to assess the cAMP-regulated chloride (Cl) ion transport properties of freshly excised nasal mucosa from PCD compared with normal and chronic rhinosinusitis (CRS). Study Design Electrophysiology study utilizing Ussing type hemi-chamber technique with three different types of nasal tissue (normal, CRS, PCD) obtained from patients during endoscopic surgery at tertiary referral center. Methods Nasal tissues were examined under short-circuit conditions and gradient-driven Cl currents were continuously recorded. The cAMP elevating agonist (forskolin) was added to stimulate CFTR-mediated Cl secretion. To prevent misinterpretation of flux measurement, Cl transport inhibitors were used at the end of all experiments. Basal Cl currents (ICl) and changes in IClto forskolin (ΔICl) were compared between normal, CRS and PCD nasal tissues. Results Forskolin stimulated Cl currents across all different types of nasal epithelia. The Cl secretory response was effectively blocked by the Cl ion transport inhibitors. ICl were significantly higher in normals (155.0 ± 9.3μA/cm2) compared to CRS (79.1 ± 15.0μA/cm2) and PCD (70.9 ± 20.4μA/cm2) (p = 0.005). ΔICl in CRS (14.8 ± 2.3μA/cm2) and PCD (12.2 ± 2.4μA/cm2) were markedly diminished compared to normals (28.3 ± 4.7μA/cm2) (p = 0.024). Conclusions PCD tissues were characterized by impaired ICl and ΔICl. Both parameters were reduced by 54.3 % and 56.9 % in PCD when compared to normals.

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Frequency of Cystic Fibrosis Transmembrane Conductance Regulator Variants in Individuals Evaluated for Primary Ciliary Dyskinesia

Hannah

Truty

Gonzales

et al. 2019

The Journal of Pediatrics

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Carrier status for 3 most frequentCFTR mutations in Polish PCD/KS patients: lack of association with the primary ciliary dyskinesia phenotype

Cited by 4 publications

References 17 publications

Mutations in Radial Spoke Head Genes and Ultrastructural Cilia Defects in East-European Cohort of Primary Ciliary Dyskinesia Patients

Mutations in Radial Spoke Head Genes and Ultrastructural Cilia Defects in East-European Cohort of Primary Ciliary Dyskinesia Patients

Characteristics of chloride transport in nasal mucosa from patients with primary ciliary dyskinesia

Frequency of Cystic Fibrosis Transmembrane Conductance Regulator Variants in Individuals Evaluated for Primary Ciliary Dyskinesia

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