Introduction: Pathogenic variants in the OFD1 gene are linked to a spectrum of syndromes that exhibit partial clinical overlap. Hemizygous loss-of-function variants are considered lethal in males, while heterozygous loss-of-function variants generally result in oro-facial-digital syndrome type 1. A reported phenotype, Simpson–Golabi–Behmel syndrome type 2, was published once but remains controversial, with many specialists questioning its validity and arguing about its continued listing in the OMIM database. Methods: To investigate the genetic and phenotypic characteristics of the patients, we performed clinical exome sequencing, family-based genetic analysis, X-inactivation studies, electron microscopy, and detailed clinical assessments. Results: Three patients from unrelated families carrying loss-of-function variants in the OFD1 gene were identified, emphasizing the diverse phenotypic spectrum of OFD1-associated disorders. The first patient, a female with a heterozygous frameshift variant p.(Gln398LeufsTer2), was diagnosed with oro-facial-digital syndrome type 1. The second patient, a male with a heterozygous nonsense variant p.(Gln892Ter), presented with features resembling Simpson–Golabi–Behmel syndrome type 2, as previously reported under this diagnosis. The third patient, a male with another heterozygous nonsense variant p.(Glu879Ter), exhibited isolated primary ciliary dyskinesia without any syndromic features. Conclusions: This study contributes to the growing body of evidence on the expanding phenotypic spectrum of OFD1-associated disorders. It underscores the need for further investigation into the molecular mechanisms underlying the diverse presentations and the necessity of re-evaluating diagnostic classifications for conditions such as SGBS2 in the context of variants in the OFD1 gene.

Primary ciliary dyskinesia (PCD) is a rare hereditary disease from the group of ciliopathies with extensive locus and allelic heterogeneity (ORPHA 244, 98861; OMIM 242650, 244000). This disease is inherited by autosomal dominant or autosomal recessive type and, less often, by X-linked type (OMIM 300424). Retinitis pigmentosa develops in the X-linked PCD variant. The overall minimum global prevalence of PCD according to European data is 1 : 7554. There is no generally accepted classification of PCD in the international classification of diseases (ICD), 10th revision. PCD is not presented in ICD-10 as a separate medical entity, and the code Q32.4 – Other congenital bronchial anomalies – is used for coding. In the new edition of ICD-11, the code LA75.Y is highlighted – Other specified structural abnormalities of the lungs.Primary ciliary dyskinesia. However, there is no generally accepted classification of PCD. The aim of the study was to develop a classification of primary ciliary dyskinesias to improve the efficiency of medical care for patients during follow-up.Methods. European and Russian clinical recommendations, as well as ICD 10th and 11th revision, Classification of Respiratory Insufficiency (2020), Order of 27.08.19 No.585n “On classifications and criteria used in the implementation of medical and social expert assessment of citizens by federal state institutions of medical and social expert assessment” (as amended on 06.10.21) were used to create the classification.Results. The classification of PCD was created and can be recommended for use in clinical practice. The classification was based on the presence or absence of the Sievert – Kartagener syndrome (complete, not complete), as well as clinical and instrumental characterization of bronchopulmonary changes based on the presence of chronic obstructive bronchitis, bronchiectasis (specifying the type and localization), pneumofibrosis with the process activity (exacerbation, remission), and the degree of respiratory failure. It is recommended to take into account extrapulmonary manifestations of PCD, such as rhinosinusitis, media otitis, congenital heart defect, and complications. It is recommended to use the PICADAR (PrImary CiliAry DyskinesiA Rule) score and to include the results of video microscopy, DNA diagnosis, and microbiological examination in the diagnosis.Conclusion. The application of the proposed classification can be useful in the dynamic observation of the patient, therapy and in the conduct of medical and social expert assessment.

Primary ciliary dyskinesia (PCD) (Online Mendelian Inheritance in Man - OMIM - #242650) is a rare hereditary disease, which is based on a defect in the ultrastructure of the cilia epithelium of the respiratory tract which leads to the motor function disorder. Data about health characteristics of patients with PCD in the Russian Federation are incomplete.The aim of the study was to investigate the clinical, laboratory, and instrumental characteristics of patients with PCD.Methods. The data of 90 patients (22 adults (24.4%) and 68 children (75.6%)) from several medical centers were studied. The following methods were used: medical history, spirometry, microbiological examination of the respiratory tract, video microscopic analysis of the functional activity of the nasal mucosa ciliated epithelium, transmission electron microscopy of the ciliated epithelium, and DNA testing.Results. The median age at diagnosis was 17.0 years for adults and 5.0 years for children. Kartagener syndrome was detected in 23 (27%) people, including 6 (26.0%) adults. Hearing loss was noted in 5 (26.3%) adult patients and 15 (26.8%) children. Light microscopy of the ciliated epithelium was performed in 14 (82.3%) children and 3 (17.7%) adults. In 12 patients, cilia motor activity was not registered at each of the magnifications (x 100, x 400, x 1,000). Transmission electron microscopy showed that absence ofinternal and external dynein handles (51%) and absence of internal dynein handles (17.9%) were the most common disorders. DNA testing was performed in 55 (61.2%) patients: 16 (29.1%) adults and 38 (70.9%) children. The most common genetic variants were found in the DNAH5 and HYDIN genes. Lung function was reduced in both adults and children, but a significant decrease was noted in adult patients. P. aeruginosa predominated in the culture and accounted for 21.3% (intermittent detection in 13.2%, persistent detection in 9%). It has increased resistance to antibiotics.Conclusion. The results correlate with the European data. Infection caused by P. aeruginosa with the increased resistance to antibiotics was prevalent in patienths with PCD.

Primary ciliary dyskinesia (PCD) is a rare hereditary disease, a ciliopathy that is based on a defect in the ultrastructure of the cilia of the epithelium of the respiratory tract and similar structures. All parts of the respiratory tract are affected. About half of the patients with PCD have transposition of the internal organs (Kartagener syndrome – KS).The aim was to investigate the clinical and genetic characteristics of patients with PCD with and without KS.Methods. An assessment of clinical and genetic characteristics was performed in a sample of 127 patients with PCD, who were divided into 2 groups: patients with KS (n = 60) and without KS (n = 67). The groups were compared on the basis of their medical history (according to the PICADAR scale), clinical, instrumental and laboratory data, including the results of light and video microscopy, transmission electron microscopy (TEM) and genetic testing.Results. According to the results of comparative characterization of patients with PCD with and without KS, there were similarities in the medical history, decreased lung function indices, videomicroscopy results – ciliated epithelium beating below 6 Hz, TEM – predominance of dynein arm defect. The PICADAR score was higher in the group with KS than in the group without it; congenital heart defects and renal pathology were found more frequently in patients with KS, while hearing loss and nasal polyposis were found more frequently in patients without KS. Electron microscopy revealed defects in the outer and inner dynein arms of the cilia in 50% of patients in both groups, and a tendency to lack of the central pair of microtubules in 18% of patients without KS. The following genes responsible for PCD were found in both groups: DNAH5, CFAP300 and HYDIN. DNAH5 gene variants were more common for KS patients (61.1%), while HYDIN gene variants were only found in patients with PCD without KS (15.8%).Conclusion. The identified differences may help in the diagnosis of the groups studied.

Primary ciliary dyskinesia (PCD) is a rare hereditary disease. In this ciliopathy, the disturbed structure and motility of the ciliary epithelium negatively affects the ciliary function and leads to prominent decrease or absence of mucociliary clearance. The European guidelines recommend analyzing the cilia beat frequency (СBF) in a native preparation or in ALI culture using light microscopy as one of the methods to confirm the diagnosis of PCD.The aim of this project was to create software for automated analysis of the movement/beating of the ciliary epithelium of the respiratory tract for the diagnosis of primary ciliary dyskinesia using digital high-speed video microscopy in vivo and in vitro.Methods. Five healthy donors and 10 patients with suspected PCD underwent nasal epithelial brush biopsy. The preparations were examined with a transmission electron microscope in vivo. Epithelial cells were also isolated from the nasal biopsy specimen, and ciliogenesis of these cells was performed by ALI-culturing, followed by digital high-speed video microscopy and assessment of the number of active cells and cilia beating frequency. The resulting video images were used to create the software.Results. Software for determination of ciliary epithelium beat frequency in primary ciliary dyskinesia (PCD HighSpeed Video Microscopy Analysis – PCD HSVMA) was created to optimize the diagnosis of PCD by light microscopy (software registration number 2023687245). The software is designed to count the number of active cells of ciliary epithelium and CBF (Hz) by digital high-speed video microscopy in vivo and in vitro in ALI-culture. PCD HSVMA software features storage of patient data, display of heat map, formation of a large server database of patients and video files, building of color and static histograms, processing of several areas in one video. Our software has a number of advantages over CiliarMove and Cilialyzer and has high correlation of CFB (Hz) estimation with these products.Conclusion. Our software can be used for improvement of PCD diagnostics in laboratories of healthcare institutions, in scientific institutions and can be included in specialist educational programs for laboratory doctors, pediatricians, general practitioners, pulmonologists, diagnosticians (endoscopists).

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired mucociliary clearance due to defects in motile cilia. This study investigates the impact of loss-of-function mutations in the CFAP300 gene on the ciliary structure and function in three PCD patients. Using a multimodal approach, we integrated molecular genetic testing, transmission electron microscopy, the high-speed video microscopy assay and immunofluorescence staining to analyze ciliary motility and protein expression in both ex vivo and in vitro-obtained ciliary cells. Our results revealed that the pathogenic variant c.198_200delinsCC (p.Phe67ProfsTer10) in CFAP300 led to the absence of the functional CFAP300 protein, the complete loss of outer and inner dynein arms and immotile cilia. Air–liquid interface (ALI)-cultured cells from patients exhibited no ciliary beating, contrasting with healthy controls. Immunostaining confirmed the absence of CFAP300 in patient-derived cilia, underscoring its critical role in dynein arm assembly. These findings highlight the diagnostic utility of ALI cultures combined with functional and protein analyses for PCD, offering a clinically actionable framework that can be readily incorporated into standard diagnostic workflows.