Type II Gaucher Disease: Compound Heterozygote with RecNciI and L444P Mutations

Wahab, Atqah Abdul; Thani, G. Al; Dawod, S. T.; Kambouris, Marios; Hamed, Moath

doi:10.1093/tropej/47.2.110

Cited by 17 publications

(16 citation statements)

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“…Some reports have been published about CF patients in the Middle East [9,10] [16–28] . These reports showed the following frequencies, 1:5800 in Bahrain [19] , 1:2650 in Jordan, 1:2560 in Kuwait [20] , and 1: 15,876 in United Arab Emirates [21] .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there are mutations that appear to be more widely spread throughout the Middle East but are rarely observed elsewhere. In some cases, these more frequent mutations may be specific for a subset of the people in the Middle East defined by a common ethnic or religious background, e.g., the 1548delG mutation in Saudi Arabia [18,26] , Bedouin tribes in the case of I1234V [27] , the S549R (T > G) mutation in Bedouins from the United Arab Emirates and Oman [21] , and the 548A > T mutation in Bahrain [28] .…”

Section: Discussionmentioning

confidence: 99%

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Profile of cystic fibrosis in a single referral center in Egypt

El-Falaki

Shahin

ElBasha

et al. 2014

Journal of Advanced Research

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It was generally believed that Cystic fibrosis (CF) is rare among Arabs; however, the few studies available from Egypt and other Arabic countries suggested the presence of many undiagnosed patients. The aim of the present study was to determine the frequency of CF patients out of the referred cases in a single referral hospital in Egypt. A total of 100 patients clinically suspected of having CF were recruited from the CF clinic of the Allergy and Pulmonology Unit, Children’s Hospital, Cairo University, Egypt, throughout a 2 year period. Sweat chloride testing was done for all patients using the Wescor macroduct system for collection of sweat. Quantitative analysis for chloride was then done by the thiocyanate colorimetric method. Patients positive for sweat chloride (⩾60 mmol/L) were tested for the ΔF508 mutation using primer specific PCR for cystic fibrosis transmembrane conductance regulator (CFTR) gene. Thirty-six patients (36%) had a positive sweat chloride test. The main clinical presentations in patients were chronic cough in 32 (88.9%), failure to thrive in 27 (75%), steatorrhea in 24 (66.7%), and hepatobiliary involvement in 5 (13.9%). Positive consanguinity was reported in 50% of CF patients. Thirty-two patients were screened for ΔF508 mutation. Positive ΔF508 mutation was detected in 22 (68.8%) patients, 8 (25%) were homozygous, 14 (43.8%) were heterozygous, and 10 (31.3%) tested were negative. CF was diagnosed in more than third of patients suspected of having the disease on clinical grounds. This high frequency of CF among referred patients indicates that a high index of suspicion and an increasing availability of diagnostic tests lead to the identification of a higher number of affected individuals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Profile of cystic fibrosis in a single referral center in Egypt

El-Falaki

Shahin

ElBasha

et al. 2014

Journal of Advanced Research

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“…We sought to confirm previously-identified coupled residues in NBD2 and, more importantly, to identify any potential changes in the predicted co-evolved network in response to disease-causing, or associated mutations. We chose to focus on four mutations (N1303K, S1235R, S1251N, and D1270N) based on prevalence in CF population, and varying clinical outcomes [27][28][29][30][31][32]. The N1303K mutation is the most frequent CF-causing mutation in Europe (7.8% in southwestern France), and patients have severe clinical outcomes such as pancreatitis, pulmonary complications, and diabetes mellitus [11,27].…”

Section: Introductionmentioning

confidence: 99%

Disease-relevant mutations alter amino acid co-evolution networks in the second nucleotide binding domain of CFTR

Ivey

Youker

2020

PLoS ONE

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Cystic Fibrosis (CF) is an inherited disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Mutations in CFTR cause impaired chloride ion transport in the epithelial tissues of patients leading to cardiopulmonary decline and pancreatic insufficiency in the most severely affected patients. CFTR is composed of twelve membrane-spanning domains, two nucleotide-binding domains (NBDs), and a regulatory domain. The most common mutation in CFTR is a deletion of phenylalanine at position 508 (ΔF508) in NBD1. Previous research has primarily concentrated on the structure and dynamics of the NBD1 domain; However numerous pathological mutations have also been found in the lesser-studied NBD2 domain. We have investigated the amino acid coevolved network of interactions in NBD2, and the changes that occur in that network upon the introduction of CF and CF-related mutations (S1251N(T), S1235R, D1270N, N1303K (T)). Extensive coupling between the α-and β-subdomains were identified with residues in, or near Walker A, Walker B, H-loop and C-loop motifs. Alterations in the predicted residue network varied from moderate for the S1251T perturbation to more severe for N1303T. The S1235R and D1270N networks varied greatly compared to the wildtype, but these CF mutations only affect ion transport preference and do not severely disrupt CFTR function, suggesting dynamic flexibility in the network of interactions in NBD2. Our results also suggest that inappropriate interactions between the β-subdomain and Q-loop could be detrimental. We also identified mutations predicted to stabilize the NBD2 residue network upon introduction of the CF and CF-related mutations, and these predicted mutations are scored as benign by the MUTPRED2 algorithm. Our results suggest the level of disruption of the coevolution predictions of the amino acid networks in NBD2 does not have a straightforward correlation with the severity of the CF phenotypes observed.

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“…[ 1 2 ] CFTR I 1234 mutation is one of the common mutations found in the Arabian Gulf region and is associated with pancreatic insufficiency. [ 3 ] Early manifestations include mucosal glandular hypertrophy, depletion of airway's surface fluid, and ineffective clearance of mucus. These changes further lead to airway obstruction, airway inflammation, infection, and regional air trapping.…”

Section: Introductionmentioning

confidence: 99%

HRCT in cystic fibrosis in patients with CFTR I1234V mutation: Assessment of scoring systems with low dose technique using multidetector system and correlation with pulmonary function tests

Bhat

Wahab²,

Garg³

et al. 2015

Indian Journal of Radiology and Imaging

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Background and Aims:Pulmonary changes in patients with cystic fibrosis (CF) with CFTR I1234V mutation have not been extensively documented. Impact of geographic influence on phenotypical expression is largely unknown. This descriptive clinical study presents the high-resolution computed tomography (HRCT) pulmonary findings and computed tomography (CT) scoring with respect to pulmonary function tests (PFT) in a small subset of CF group.Materials and Methods:We examined 29 patients between 2 and 31 years of age with CFTR I1234V mutation. HRCT and PFT were performed within 2 weeks of each other. Imaging abnormalities on HRCT were documented and analyzed by utilizing the scoring system described by Bhalla et al., Brody et al., Helbich et al.,and Santamaria et al. Efficacy of the scoring system with respect to PFT was compared.Statistical Analysis:Inter-observer reliability of the scoring systems was tested using intraclass correlation (ICC) between the two observers. Spearman correlation coefficients were calculated between the scoring systems and between the scoring systems and PFT results.Results:In our study, right upper and middle lobes were the most frequently involved sites of involvement. Bronchiectasis and peribronchial thickening were the most frequent imaging findings. Scores with all four scoring systems were reproducible, with good ICC coefficient of 0.69. There was good agreement between senior radiologists in all scoring systems.Conclusion:We noted pulmonary imaging abnormalities in a large majority (96%) of our CF patients. There was no significant difference in the CT scores observed from various systems. The CT evaluation system by Broody is detailed and time consuming, and is ideal for research and academic setup. On the other hand, the systems by Bhalla and Santamaria are easy to use, quick, and equally informative. We found the scoring system by Santamaria preferable over that of Bhalla by virtue of additional points of evaluation and ease of use, and therefore better suited for busy clinical practice.

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Type II Gaucher Disease: Compound Heterozygote with RecNciI and L444P Mutations

Cited by 17 publications

References 0 publications

Profile of cystic fibrosis in a single referral center in Egypt

Profile of cystic fibrosis in a single referral center in Egypt

Disease-relevant mutations alter amino acid co-evolution networks in the second nucleotide binding domain of CFTR

HRCT in cystic fibrosis in patients with CFTR I1234V mutation: Assessment of scoring systems with low dose technique using multidetector system and correlation with pulmonary function tests

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