Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

Fassad, Mahmoud R; Shoman, Walaa; Morsy, Heba; Patel, Mitali; Radwan, Nesrine; Jenkins, Lucy; Cullup, Thomas; Fouda, Eman; Mitchison, Hannah M.; Fasseeh, Nader

doi:10.1111/cge.13661

Cited by 25 publications

(22 citation statements)

References 29 publications

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“…In a recent large cohort study conducted in Saudi Arabia, this variant was the most common, which accounted for 34% of families with molecularly confirmed PC, even though it depended on WES and our results were mainly through gene panels [ 14 ]. It is worth to mention that studies conducted in other Arab countries with different ancestries (Egypt and Tunisia) reported CCDC39 as the most commonly involved gene in their population [ 15 , 16 ]. This is in contrast to the American Thoracic Society report of DNAH5 and DNI1 being the most common genes associated with PCD [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular characteristics of primary ciliary dyskinesia

Alzaid¹,

Al-Mobaireek

Almannai³

et al. 2021

International Journal of Pediatrics and Adolescent Medicine

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Background Primary ciliary dyskinesia (PCD) is a ciliopathy with diverse clinical and genetic findings caused by abnormal motile cilia structure and function. In this study, we describe the clinical characteristics of confirmed PCD cases in our population and report the radiological, genetic, and laboratory findings. Methods This was a retrospective, observational, single-centre study. We enrolled 18 patients who were diagnosed with confirmed PCD between 2015 and 2019. We then analyzed their data, including clinical findings and workup. Results In our cohort, 56% of patients had molecularly confirmed PCD, and RSPH9 was the most common gene identified. Transmission electron microscopy (TEM) showed an ultrastructural defect in 64% of samples, all of which matched the genetic background of the patient. Situs inversus (SI) was observed in 50% of patients, and congenital heart disease was observed in 33%. The median body mass index (BMI) was 15.87 kg/m 2 , with a median z score of -1.48. The median FEV1 value was 67.6% (z score - 2.43). Radiologically, bronchiectasis was noted in 81% of patients at a variable degree of severity. Lung bases were involved in 91% of patients. We were unable to correlate the genotype-phenotype findings. Conclusion We describe the clinical and molecular characteristics of patients with confirmed PCD in a tertiary centre in Saudi Arabia and report 9 new pathogenic or likely pathogenic variants in one of the PCD-associated genes.

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Section: Discussionmentioning

confidence: 99%

Clinical and molecular characteristics of primary ciliary dyskinesia

Alzaid¹,

Al-Mobaireek

Almannai³

et al. 2021

International Journal of Pediatrics and Adolescent Medicine

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“…As one of more than 40 genes responsible for PCD, CCDC39-related PCD is inherited in an autosomal recessive pattern, and patients with CCDC39 variants commonly suffer from sinusitis, bronchitis, bronchiectasis, laterality defects, and infertility, among other conditions (2,21). Numerous studies have shown that variants in this gene cause PCD in patients from different geographic locations and diverse ethnic groups (10,21,(28)(29)(30). In 2010, Merveille et al firstly positionally cloned CCDC39 and reported an association between PCD and this cilia-related gene in dogs and humans (21).…”

Section: Discussionmentioning

confidence: 99%

“…Fassad et al conducted a study in a multiethnic PCD cohort from 161 unrelated families and revealed that 42% of Arab families with PCD carried CCDC39 / CCDC40 variants ( 29 ). Similarly, an investigation conducted in Egypt suggested that 7 of 33 individuals carried biallelic variants in CCDC39 / CCDC40 ( 30 ). Analysis of the genetic spectrum of Chinese children with PCD showed that 5 of 51 cases harbored biallelic variants in CCDC39 ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Biallelic Variants in CCDC39 Gene Lead to Primary Ciliary Dyskinesia and Kartagener Syndrome

Shi

Geng

et al. 2022

BioMed Research International

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Background. Primary ciliary dyskinesia (PCD) is a clinical syndrome characterized by cilia with an abnormal structure or function. Its main clinical manifestations comprise chronic bronchitis, cough, recurrent respiratory infections, situs inversus, and male infertility. Single-gene variants are widely assumed to be the main cause of this rare disease, and more than 40 genes have been described to be associated with its onset. CCDC39 is essential for assembling the inner dynein arms and dynein regulatory complex and is important in cilia motility. CCDC39 variants were reported as a monogenic etiology of PCD. Methods. This study investigated two unrelated Chinese patients diagnosed as PCD. The chest computed tomography scan was performed to identify PCD phenotypes of the two probands. Considering the effect of PCD on male fertility, routine semen analysis, sperm morphology examination, and scanning electron microscopy were performed to assess the semen characteristics of male proband in family 2 (F2 II-1), who had a history of infertility. Subsequently, the peripheral blood samples of probands were collected to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease. Results. Whole-exome sequencing revealed a homozygous CCDC39 variant in the female proband of family 1 (F1 II-1: c.286C>T:p.Arg96Ter) and two compound heterozygous CCDC39 variants in the male proband of family 2 (F2 II-1: c.732_733del: p.Ala245PhefsTer18; c.2800_2802dup:p.Val934dup). The two probands showed the typical PCD phenotypes, including chronic bronchitis, recurrent respiratory infections, and situs inversus. The male proband also showed oligoasthenoteratospermia with multiple morphological abnormalities of the sperm flagella. Additionally, CCDC39 protein level was significantly lower in the sperm of male proband than in the sperm from normal controls. Conclusion. We identified a homozygous variant reported previously and two compound heterozygous variants of CCDC39 possibly responsible for PCD pathogenesis, expanding the variant spectrum of Chinese PCD, Kartagener syndrome, and morphological abnormalities of the sperm flagella involving CCDC39.

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“…To our surprise, no patient had homozygous or compound heterozygous variations in DNAI1 in our cohort study. CCDC39 and CCDC40 are the most prevalent mutated genes in individuals of Egyptian origin with PCD [ 29 ]. A comparable phenomenon was observed in 58 Tunisian patients with PCD in whom CCDC39 and c.2190del in CCDC39 was a mutation hotspot, whereas deleterious mutations in CCDC39 or CCDC40 were rarely observed in Chinese patients with PCD and only one case involved CCDC40 dysfunction [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia

Zhao

Bian

Liu

et al. 2021

Orphanet J Rare Dis

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Background Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for diagnosis, such as nasal nitric oxide measurement and digital high-speed video microscopy with ciliary beat pattern analysis, can be expensive or unavailable. To confirm PCD diagnosis, we used a strategy combining assessment of typical symptoms with whole-exome sequencing (WES) and/or low-pass whole-genome sequencing (WGS) as an unbiased detection tool to identify known pathogenic mutations, novel variations, and copy number variations. Results A total of 26 individuals of Chinese origin with a confirmed PCD diagnosis aged 13 to 61 years (median age, 24.5 years) were included. Biallelic pathogenic mutations were identified in 19 of the 26 patients, including 8 recorded HGMD mutations and 24 novel mutations. The detection rate reached 73.1%. DNAH5 was the most frequently mutated gene, and c.8383C > T was the most common mutated variant, but it is relatively rare in PCD patients from other ethnic groups. Conclusion This study demonstrates the practical clinical utility of combining WES and low-pass WGS as a no-bias detecting tool in adult patients with PCD, showing a clinical characteristics and genetic spectrum of Chinese PCD patients.

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Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

Cited by 25 publications

References 29 publications

Clinical and molecular characteristics of primary ciliary dyskinesia

Clinical and molecular characteristics of primary ciliary dyskinesia

Biallelic Variants in CCDC39 Gene Lead to Primary Ciliary Dyskinesia and Kartagener Syndrome

Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia

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