Primary ciliary dyskinesia among Arabs: Where do we go from here?

Hammoudeh, Samer; Gadelhak, Wessam; Janahi, Ibrahim

doi:10.1016/j.prrv.2018.09.002

Cited by 11 publications

(14 citation statements)

References 39 publications

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“…However, with limited resources, countries have additional difficulty because of the need for expensive equipment and highly trained professionals [ 17 ], and many regions of the world still suffer from a probably underestimated number of cases [ 27 ]. It was established that in European countries, the number of diagnosed cases and the age at diagnosis correlated with the government’s health expenditure [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital

Toro

Ribeiro

Marson

et al. 2022

Genes

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Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20/37 (54.1%) had chronic rhinosinusitis, 28/37 (75.6%) had bronchiectasis, and 29/37 (78.4%) had recurrent pneumonia. A total of 17/37 (45.9%) individuals had transmission electron microscopy or genetic confirmation of PCD; 10 individuals had at least one positive pathogenic genetic variant in the PCD-related genes; however, only seven patients presented a conclusive result according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with two pathogenic variants in homozygous or compound heterozygous. The median age at diagnosis was 13 years, and the median time between suspicion and diagnosis was four years. Sixteen patients had class I electron microscopy alterations, seven had class II alterations, and 14 had normal transmission electron microscopy according to the international consensus guideline for reporting transmission electron microscopy results in the diagnosis of PCD (BEAT-PCD TEM Criteria). Genetic screening for pathogenic variants in PCD-related genes and transmission electron microscopy can help determine the PCD diagnosis; however, they are still unavailable to all individuals with clinical suspicion in Brazil. We described ultrastructural alterations found in our population along with the identification of pathogenic variants in PCD-related genes.

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Section: Discussionmentioning

confidence: 99%

Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital

Toro

Ribeiro

Marson

et al. 2022

Genes

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“…Thus, studies that catalogue variations in the community are of importance, especially in regions of a high rate of consanguinity that potentially exacerbates the prevalence of recessive disorders. This holds true for PCD, where the diagnosis still remains challenging [ 26 ]. Thus, this study describes the variations in PCD-related genes identified through a retrospective chart review of patients at a tertiary hospital in the UAE.…”

Section: Discussionmentioning

confidence: 99%

“…Founder mutations and autosomal recessive disorders are exceptionally common in the UAE due to consanguineous marriages [ 23 ]. The genetics of PCD in this population have been reviewed [ 24 , 25 , 26 , 27 , 28 , 29 ]. Higher prevalence has been reported among Arabs [ 5 ], including variants found in the United Arab Emirates (UAE), such as those involving the RSPH9 and RSPH4A genes [ 27 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…Higher prevalence has been reported among Arabs [ 5 ], including variants found in the United Arab Emirates (UAE), such as those involving the RSPH9 and RSPH4A genes [ 27 , 29 ]. Nevertheless, research involving PCD in the Arab world is still limited [ 26 ], and further population studies are highly justified. This report assesses the pathogenicity of variants in PCD-related genes found in native Emirati children with clinically significant respiratory problems.…”

Section: Introductionmentioning

confidence: 99%

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A Study on the Genetics of Primary Ciliary Dyskinesia

Alsamri

Alabdouli

Iram

et al. 2021

JCM

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Primary ciliary dyskinesia (PCD) is a poorly understood disorder. It is primarily autosomal recessive and is prevalent in tribal communities of the United Arab Emirates due to consanguineous marriages. This retrospective study aimed to assess the pathogenicity of the genetic variants of PCD in indigenous patients with significant clinical respiratory problems. Pathogenicity scores of variants obtained from the chart review were consolidated using the Ensembl Variant Effect Predictor. The multidimensional dataset of scores was clustered into three groups based on their pathogenicity. Sequence alignment and the Jensen–Shannon Divergence (JSD) were generated to evaluate the amino acid conservation at the site of the variation. One-hundred and twelve variants of 28 genes linked to PCD were identified in 66 patients. Twenty-two variants were double heterozygous, two triple heterozygous, and seven homozygous. Of the thirteen novel variants, two, c.11839 + 1G > A in dynein, axonemal, heavy chain 11 (DNAH11) and p.Lys92Trpfs in dynein, axonemal, intermediate chain 1 (DNAI1) were associated with dextrocardia with situs inversus, and one, p.Gly21Val in coiled-coil domain-containing protein 40 (CCDC40), with absent inner dynein arms. Homozygous C1orf127:p.Arg113Ter (rs558323413) was also associated with laterality defects in two related patients. The majority of variants were missense involving conserved residues with a median JSD score of 0.747. Homology models of two deleterious variants in the stalk of DNAH11, p.Gly3102Asp and p.Leu3127Arg, revealed structural importance of the conserved glycine and leucine. These results define potentially damaging PCD variants in the region. Future studies, however, are needed to fully comprehend the genetic underpinnings of PCD.

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“…PCD is often underdiagnosed, and it is estimated to occur in 1/15,000-20,000 individuals [2][3]. Moreover, due to the high consanguinity rates, PCD is more common in Arab societies, although little is known about its actual prevalence and characteristics [4]. Patients with PCD may present with neonatal respiratory distress and/or laterality defects in about half of the cases.…”

Section: Introductionmentioning

confidence: 99%

An Unusual Cause of Respiratory Distress in Term Neonate

Alallah¹,

Makki²,

Saber³

et al. 2022

Cureus

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We report a female infant who was born at 41+6 weeks of gestation to a consanguineous parent, and the initial newborn examination was within normal. At 12 hours of age, she developed tachypnea; with desaturation, she had continuous thick whitish oral secretion. Admitted to the neonatal intensive care unit (NICU) for further management, her initial blood investigation, including blood gas and chest X-ray, was normal. Due to the persistent unexplained respiratory distress with a normal chest X-ray, we obtained a further history from parents with three siblings with respiratory symptoms but no definitive diagnosis. The genetic testing of whole-exome sequences (WES) confirmed a homozygous variant c.804_806del, p. (Lys268del) in the RSPH9 gene that causes primary ciliary dyskinesia (PCD). Her three siblings were tested and found to have the same genetic mutation.

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Primary ciliary dyskinesia among Arabs: Where do we go from here?

Cited by 11 publications

References 39 publications

Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital

Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital

A Study on the Genetics of Primary Ciliary Dyskinesia

An Unusual Cause of Respiratory Distress in Term Neonate

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