Dler N O O R U L D E E N Chalabi (original) (raw)
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Med Genet, 2021
We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its g... more We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause. Methods Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed. Results We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant AGR2 transcripts caused by an intronic variant and complete absence of AGR2 transcripts caused by the large gene deletion, resulting in loss of function (LoF). Furthermore, transcriptome analysis identified significant downregulation of components of the mucociliary machinery (intraciliary transport, cilium organisation), as well as upregulation of immune processes. Conclusion We describe a previously unrecognised autosomal recessive disorder caused by AGR2 variants. AGR2-related disease should be considered as a differential diagnosis in patients presenting a CF-like phenotype. This has implications for the molecular diagnosis and management of these patients. AGR2 LoF is likely the disease mechanism, with consequent impairment of the mucociliary defence machinery. Future studies should aim to establish a better understanding of the disease pathophysiology and to identify potential drug targets.
Gastroenterology Rev , 2023
Introduction: Ingestion of foreign bodies is a significant problem among children, which necessit... more Introduction: Ingestion of foreign bodies is a significant problem among children, which necessitates early intervention and may lead to serious morbidity and even mortality. Aim: To estimate the pattern of foreign body ingestion among children and identify the role of management and its outcomes in relation to the type and site of foreign bodies. Material and methods: Our study was carried out on patients who attended the Emergency Department of the Rapareen Teaching Hospital for Paediatrics in Erbil city and were referred to the Paediatric Gastroenterology Unit during between March 2019 and January 2023. All clinical and demographic data were entered and then analysed using SPSS. Results: Fifty-four patients visited or were admitted to the Rapareen Hospital Emergency Department with a history of ingestion of foreign bodies, with a median age of 4 years (mean age: 4.14 ±2.15 years) and a nearly equal male-to-female ratio (1.16 : 1). Most of the foreign bodies were radiopaque, and the majority were located in the oesophagus at the time of initial presentation. Disc batteries (27.8%) were the commonest foreign body, followed by coins (20.4%), of which 66.7% were retrieved endoscopically, while 4 patients needed surgical intervention. Cross-tabulation reveals a significant association between the site of materials and the early presentation, type of object, and outcome. Also, a significant association was established between the type of foreign body and gender, age, time of presentation, and outcome. Conclusions: The button battery was the most common foreign body ingested among the children, and the majority were located in the oesophagus and extracted by endoscopy.
Med Genet, 2021
We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its g... more We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause. Methods Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed. Results We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant AGR2 transcripts caused by an intronic variant and complete absence of AGR2 transcripts caused by the large gene deletion, resulting in loss of function (LoF). Furthermore, transcriptome analysis identified significant downregulation of components of the mucociliary machinery (intraciliary transport, cilium organisation), as well as upregulation of immune processes. Conclusion We describe a previously unrecognised autosomal recessive disorder caused by AGR2 variants. AGR2-related disease should be considered as a differential diagnosis in patients presenting a CF-like phenotype. This has implications for the molecular diagnosis and management of these patients. AGR2 LoF is likely the disease mechanism, with consequent impairment of the mucociliary defence machinery. Future studies should aim to establish a better understanding of the disease pathophysiology and to identify potential drug targets.
Gastroenterology Rev , 2023
Introduction: Ingestion of foreign bodies is a significant problem among children, which necessit... more Introduction: Ingestion of foreign bodies is a significant problem among children, which necessitates early intervention and may lead to serious morbidity and even mortality. Aim: To estimate the pattern of foreign body ingestion among children and identify the role of management and its outcomes in relation to the type and site of foreign bodies. Material and methods: Our study was carried out on patients who attended the Emergency Department of the Rapareen Teaching Hospital for Paediatrics in Erbil city and were referred to the Paediatric Gastroenterology Unit during between March 2019 and January 2023. All clinical and demographic data were entered and then analysed using SPSS. Results: Fifty-four patients visited or were admitted to the Rapareen Hospital Emergency Department with a history of ingestion of foreign bodies, with a median age of 4 years (mean age: 4.14 ±2.15 years) and a nearly equal male-to-female ratio (1.16 : 1). Most of the foreign bodies were radiopaque, and the majority were located in the oesophagus at the time of initial presentation. Disc batteries (27.8%) were the commonest foreign body, followed by coins (20.4%), of which 66.7% were retrieved endoscopically, while 4 patients needed surgical intervention. Cross-tabulation reveals a significant association between the site of materials and the early presentation, type of object, and outcome. Also, a significant association was established between the type of foreign body and gender, age, time of presentation, and outcome. Conclusions: The button battery was the most common foreign body ingested among the children, and the majority were located in the oesophagus and extracted by endoscopy.