Clinical and molecular characteristics of primary ciliary dyskinesia

Alzaid, Mohammed; Al-Mobaireek, Khalid; Almannai, Mohammed; Mukhtar, Gawahir; Eltahir, Safa; Zafar, Adnan; Zada, Abdulali P.; Alotaibi, Wadha

doi:10.1016/j.ijpam.2021.03.002

Cited by 6 publications

(5 citation statements)

References 39 publications

(52 reference statements)

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“…Regarding TEM findings, in contrast to the current study that showed ODA loss and MTD + IDA loss to be equally the most common hallmark defects, ODA + IDA loss was the most common hallmark defect reported in previous studies in the Kingdom of Saudi Arabia (KSA), Oman, and Iran 32–34 . ODA absence as a Class 1 hallmark defect was not reported among the Iranian cohort 34 …”

Section: Discussioncontrasting

confidence: 99%

“…Similarly, previous studies in Tunisia and Palestine reported the same gene to be the most frequently mutated in their cohorts (>50% and 26%, respectively). 42,43 In a study carried out in KSA, RSPH9 was the most frequently affected gene (34%), 32 while in a Turkish study, DNAH5 was the most commonly mutated gene (26.1%). 44 In the current study, none of the variants showed any founder effect which could have been used in any future PCD genetic screening.…”

Section: Discussionmentioning

confidence: 99%

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Primary ciliary dyskinesia in Egypt: First report of cilia ultrastructural defects and novel genetic variants

Shoman,

Elbanna,

Fassad

et al. 2024

Pediatric Pulmonology

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BackgroundPrimary ciliary dyskinesia (PCD) is a genetic disorder that follows several inheritance patterns predominately autosomal recessive. It is caused by aberrant motile cilia structure and/or function. Diagnosis of PCD is challenging, involving complex technical steps and requiring special expertise. Here, we report the first attempt to employ transmission electron microscopy (TEM) to precisely diagnose PCD in Egypt. The study aims to outline the findings of diagnostic procedures, including TEM and genetic analysis, carried out on a cohort of Egyptian patients clinically suspected of having PCD.MethodsA cohort of 48 individuals underwent testing to determine their PCD status. The diagnostic modalities used included genetic and TEM analysis. Clinical features and diagnostic test outcomes were described.ResultsPCD was confirmed in 27 of the 48 participating cases. Class 1 hallmark defects were the most commonly detected TEM findings. Outer dynein arm defect in addition to microtubular disorganization with inner dynein arm loss was found equally to be the most common diagnostic defects in the confirmed cases. A highly heterogeneous genetic background was found with 14 different affected genes. Of these, CCDC39 was the most commonly mutated one. The variants, c.430‐1G>A in DNAAF6, c.8099C>T in DNAH11, c.263T>C in DNAL1, c.1154dup in NEK10, c.487C>T in HYDIN, and c.90+1G>C in CCDC39 gene were detected novel variants.ConclusionDiagnosis of PCD is challenging especially in low‐ and middle‐income countries. As there is no single reference diagnostic test, integrating diagnostic modalities, such as TEM and genetics, can enhance diagnosis.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Primary ciliary dyskinesia in Egypt: First report of cilia ultrastructural defects and novel genetic variants

Shoman,

Elbanna,

Fassad

et al. 2024

Pediatric Pulmonology

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“…In a cohort from Tunisia (34 families), CCDC39 was the most common gene (44.1%) similar to our population, followed by DNAH5 (11.8%), HYDIN (8.8%) and TTC25 (5.9%) (36). In Saudi Arabia the most commonly mutated gene was RSPH9 among 18 cases, which included the RSPH9 c.800-802del mutation also reported here (37).…”

Section: Discussionsupporting

confidence: 81%

The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum

et al. 2023

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Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic, and clinical spectrum of the Palestinian PCD population.Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM), and/or PCD genetic panel or whole exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including FEV1GLI z-scores, and BMI z-scores.Sixty-eight individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. Forty-five individuals from 40 families had seventeen clinically actionable variants, and 4 had variants of unknown significance in 14 PCD-genes. CCDC39, DNAH11, andDNAAF11were the most commonly mutated genes. 100% of variants were homozygous. Patients had median age of 11.2 years at diagnosis, were highly consanguineous (93%) and 100% of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%), and situs inversus(43%). Lung function at diagnosis was already impaired (FEV1z-score median −1.90 (−5.0 to 1.32)) and growth was mostly within the normal range (z-score mean= −0.36 (−3.03 to 2.57). 19% individuals had finger clubbing.Despite limited local resources, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity.

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“…It is important to do regular lung function assessments in children with PCD as this will pick up the decline in lung function at an early stage 7 . Sinopulmonary infections in PCD involve mucous impaction because of the underlying ciliary defects, and the extent of ciliary dysfunction depends on the type of genetic mutation 8 . There is significant heterogeneity in the disease spectrum due to underlying genetic defect 9 as children with genetic variants in DNAH11, DNAH9, and RSPH1 mutations have milder respiratory phenotypes 10–12 .…”

Section: Introductionmentioning

confidence: 99%

“…7 Sinopulmonary infections in PCD involve mucous impaction because of the underlying ciliary defects, and the extent of ciliary dysfunction depends on the type of genetic mutation. 8 There is significant heterogeneity in the disease spectrum due to underlying genetic defect 9 as children with genetic variants in DNAH11, DNAH9, and RSPH1 mutations have milder respiratory phenotypes. [10][11][12] Children with genetic variants in CCDC39 and CCDC40 have greater nutritional and lung impairment and early lung decline.…”

mentioning

confidence: 99%

In children with primary ciliary dyskinesia, which type of lung function test is the earliest determinant of decline in lung health: A systematic review

Zafar

Hall

2022

Pediatric Pulmonology

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Background: Primary ciliary dyskinesia is a rare genetic disorder characterized by recurrent sinopulmonary infections and worsening obstructive lung disease. Kidney and brain involvement is less common and is associated with overlapping ciliopathies/syndromes. The lungs are impacted early in the course of the disease, so it is vital to monitor lung function and recognize any decline by doing appropriate lung function tests. This systematic review compares different lung function tests and analyzes which one becomes abnormal earlier in the disease.Methods: A systematic review was conducted following the methodology in the "Cochrane Handbook on Systematic Reviews for diagnostic tests." The Preferred Reporting Items for Systematic Review and Meta-Analyses were used to report the results. The risk of bias assessment was done using "The Cochrane Handbook for Systematic Reviews tool for interventional studies." A meta-analysis was not performed due to the small sample size. All studies were analyzed by using Joanna Briggs Institute's critical appraisal tool.Results: After screening for the duplication of results and applying inclusion and exclusion criteria, 14 studies were assessed by reading the full texts. Out of these, eight were finally included in this systematic review. The total sample size from all studies was 165, including 80 males. All the studies used spirometry as a lung function test, whereas multiple breath washout was used in five studies. Other tests used for comparison were computed tomography (CT), magnetic resonance imaging (MRI), cardiopulmonary exercise testing, 6-min walk test, DLCO, maximal inspiratory pressure, maximal expiratory pressure, and PaO 2 . Lung clearance index (LCI) by multiple breath washout had a stronger association with the structural changes on CT/MRI than spirometry indices like forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25% to 75% of lung volume .Conclusions: Based on the evidence from this systematic review, LCI becomes abnormal earlier than FEV1 or FEF 25-75 and positively correlates with the findings

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Clinical and molecular characteristics of primary ciliary dyskinesia

Cited by 6 publications

References 39 publications

Primary ciliary dyskinesia in Egypt: First report of cilia ultrastructural defects and novel genetic variants

Primary ciliary dyskinesia in Egypt: First report of cilia ultrastructural defects and novel genetic variants

The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum

In children with primary ciliary dyskinesia, which type of lung function test is the earliest determinant of decline in lung health: A systematic review

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