7 research outputs found
Natural history, with clinical, biochemical and molecular characterization, of classical homocystinuria in the Qatari population
Classical homocystinuria (HCU) is the most common inborn error of metabolism in Qatar, with an incidence of 1:1800, and is caused by the Qatari founder p.R336C mutation in the CBS gene. This study describes the natural history and clinical manifestations of HCU in the Qatari population. A single center study was performed between 2016 and 2017 in 126 Qatari patients, from 82 families. Detailed clinical and biochemical data were collected and Stanford-Binet intelligence, quality of life and adherence to treatment assessments were conducted prospectively. Patients were assigned to one of three groups, according to mode of diagnosis: 1) Late Diagnosis Group (LDG), 2) Family Screening Group (FSG), and 3) Newborn Screening Group (NSG). Of the 126 patients, 69 (55%) were in the LDG, 44 (35%) in the NSG, and 13 (10%) in the FSG. The leading factors for diagnosis in the LDG were ocular manifestations (49%), neurological manifestations (45%), thromboembolic events (4%), and hyperactivity and behavioral changes (1%). Both FSG and NSG groups were asymptomatic at time of diagnosis. NSG had significantly higher IQ, QoL, and adherence values compared with the LDG. The LDG and FSG had significantly higher Met levels than the NSG. The LDG also had significantly higher tHcy levels than the NSG and FSG. Regression analysis confirmed these results even when adjusting for age at diagnosis, current age or adherence. These findings increase understanding of the natural history of HCU and highlight the importance of early diagnosis and treatment. This article is protected by copyright. All rights reserved.Qatar National Research Fund , Grant/Award Number: 7â355â3â08
Qatar Culture Collection of Microalgae: A Sustainable Source for Biodiesel Production and Omega Fatty Acid Compounds
Microalgae are photosynthetic microorganisms that can grow in different environments (sea water, fresh water, waste water soil, rocksâŠ) and under various conditions (Light, pH, temperature, salinityâŠ). During their phases of growth, they produce a variety of metabolites such as lipids, proteins and carbohydrates in large amounts over a short period of time. These metabolites can be processed into both biofuels and other useful bioproducts. Microalgal lipids can be converted to biodiesel via process called transesterification. The use of biodiesel will decrease the emission of harmful gases, which can help in reducing the greenhouse effects and global warming. It is nontoxic, biodegradable and has the potential to replace the conventional diesel fuel. The microalgal lipids extract can also constitute a natural source of active compounds offering a variety of nutraceutical and pharmaceutical applications.
In the Algae Technologies Program at Qatar University, a Culture Collection of Cyanobacteria and Microalgae (QUCCCM) has been built and maintained in the liquid nitrogen. This culture collection contains more than 200 strains isolated during different periods of the year and from various places in Qatar. In this work we present the results of 8 marine green algae belonging to 3 different microalgal major groups: Chlorocystis sp., Nannochloris sp and Tetraselmis sp.
The strains collected from different Qatar coastal places were screened for their growth rate, amount of total lipids as well as their Fatty Acid Methyl Ester (FAMEs) profiling. Culture was done in liquid F/2 medium at 300 C for a period of 15 days, after which algae were harvested for the determination of total lipids. A one step transesterification process was used to derivitize the intrinsic lipid into fatty acid methyl esters and the individual components were identified against known standards. The fatty acid profiling was obtained using a GC-FID.
The comparative analysis of the QUCCCM isolates growth rate showed that Nannochloris sp. is the fastest growing isolate with a maximum value of 1.013 day-1. In terms of lipid contents, the results indicate a variety of the amounts. Nannochloris sp. showed the highest amount of total lipid (28.5%) followed by Chlorocystis sp. isolates with a total lipid amount of (19.5â21.5%) and later comes the Tetraselmis sp. strains with a total lipid content of (17.8â20.3%). The GC analysis showed a diverse range of FAMEs produced. All the strains screened contains the important FAMEs suitable for biodiesel production (C14, C16 and C18). The good growth rate of these strains along with their lipid content and profile make them competitive for a viable algal biofuel technology comparing to the terrestrial oil crops which need longer time to grow and present lower amount of lipids (Weyer et al., 2010). In addition, we observed the presence of the omega-3 and 9 long-chain polyunsaturated fatty acids (LC-PUFAs), such as eicosapentaenoic (EPA, 20:5 n-3), docosahexaenoic (DHA, 22:6 n-3) and Nervonic Acid (C24:1 n-9) acids, which have a high commercial value and are known for their beneficial effects on human healthqscienc
Gene therapy for spinal muscular atrophy: the Qatari experience
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by hypotonia, progressive muscle weakness, and wasting. Onasemnogene abeparvovec (ZolgensmaÂź) is a novel gene therapy medicine, FDA-approved in May 2019 for the treatment of SMA. This study aimed to describe Qatari experience with onasemnogene abeparvovec by reviewing the clinical outcomes of 9 SMA children (7 SMA type 1 and 2 with SMA type 2) aged 4â23 months treated between November 2019 and July 2020. Children Other Information Published in: Gene Therapy License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41434-021-00273-7</p
Genetic, clinical and biochemical characterization of a large cohort of patients with hyaline fibromatosis syndrome
An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome.
Au-Kline syndrome (AKS) is a neurodevelopmental disorder associated with multiple malformations and a characteristic facial gestalt. The first individuals ascertained carried de novo loss-of-function (LoF) variants in HNRNPK. Here, we report 32 individuals with AKS (26 previously unpublished), including 13 with de novo missense variants. We propose new clinical diagnostic criteria for AKS that differentiate it from the clinically overlapping Kabuki syndrome and describe a significant phenotypic expansion to include individuals with missense variants who present with subtle facial features and few or no malformations. Many gene-specific DNA methylation (DNAm) signatures have been identified for neurodevelopmental syndromes. Because HNRNPK has roles in chromatin and epigenetic regulation, we hypothesized that pathogenic variants in HNRNPK may be associated with a specific DNAm signature. Here, we report a unique DNAm signature for AKS due to LoF HNRNPK variants, distinct from controls and Kabuki syndrome. This DNAm signature is also identified in some individuals with de novo HNRNPK missense variants, confirming their pathogenicity and the phenotypic expansion of AKS to include more subtle phenotypes. Furthermore, we report that some individuals with missense variants have an "intermediate" DNAm signature that parallels their milder clinical presentation, suggesting the presence of an epi-genotype phenotype correlation. In summary, the AKS DNAm signature may help elucidate the underlying pathophysiology of AKS. This DNAm signature also effectively supported clinical syndrome delineation and is a valuable aid for variant interpretation in individuals where a clinical diagnosis of AKS is unclear, particularly for mild presentations
An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome
Abstract
Au-Kline syndrome (AKS) is a neurodevelopmental disorder associated with multiple malformations and a characteristic facial gestalt. The first individuals ascertained carried de novo loss-of-function (LoF) variants in HNRNPK. Here, we report 32 individuals with AKS (26 previously unpublished), including 13 with de novo missense variants. We propose new clinical diagnostic criteria for AKS that differentiate it from the clinically overlapping Kabuki syndrome and describe a significant phenotypic expansion to include individuals with missense variants who present with subtle facial features and few or no malformations. Many gene-specific DNA methylation (DNAm) signatures have been identified for neurodevelopmental syndromes. Because HNRNPK has roles in chromatin and epigenetic regulation, we hypothesized that pathogenic variants in HNRNPK may be associated with a specific DNAm signature. Here, we report a unique DNAm signature for AKS due to LoF HNRNPK variants, distinct from controls and Kabuki syndrome. This DNAm signature is also identified in some individuals with de novo HNRNPK missense variants, confirming their pathogenicity and the phenotypic expansion of AKS to include more subtle phenotypes. Furthermore, we report that some individuals with missense variants have an âintermediateâ DNAm signature that parallels their milder clinical presentation, suggesting the presence of an epi-genotype phenotype correlation. In summary, the AKS DNAm signature may help elucidate the underlying pathophysiology of AKS. This DNAm signature also effectively supported clinical syndrome delineation and is a valuable aid for variant interpretation in individuals where a clinical diagnosis of AKS is unclear, particularly for mild presentations