Research Title: الرواية العربية واللغة في ضوء تجربة نجيب محفوظ

Author: Muhammad Obaidellah, Published Year: 2014

مجلة كلية الآداب جامعة القاهرة, مج74، ج4،

Faculty: Arts

Abstract: ينطلق هذا البحث من تقدير مكانة اللغة في نقد العمل الأدبي، ويستند منهجيا إلى جهود ميخائيل باختين في مجال أسلوبية الرواية، وإلى جهود أخرى في مجال لسانيات الرواية كما ظهرت عند روجر فاولر. ويبرز البحث الوعي اللغوي عند محفوظ نفسه، من خلال ملاحظات متعددة للأديب الراحل عرض فيها لتجربته مع اللغة. ويذهب البحث إلى أن نجيب محفوظ سار في طريق طويل عماده تطويع اللغة التي يكتب بها لتكون لغة متناسبة مع أجواء الرواية وحاجاتها التعبيرية المتنوعة. ويتناول البحث رواية "قشتمر"/1988 حيث تبدو صنعة محفوظ فيها بشكل نموذجي، خفي، ويتأمل البحث الرواية من منظور لغوي، يعنى بالمستويات اللغوية المختلفة. ففي المستوى المعجمي يستخدم محفوظ مفردات وألفاظا تتميز بالسهولة والشيوع. وفي المستوى التركيبي يفيد من التراكيب الشفاهية مع سلامتها اللغوية وانتمائها للغة الفصحى. ويعنى البحث بإبراز الحوارية الضمنية بين هذا المستوى الشعبي والمستوى التراثي الذي ينتقيه محفوظ من ثقافته ومن البيان التقليدي أو التراثي.

Keywords: الرواية العربية، نجيب محفوظ، قشتمر، اللغة السردية

Research Title: صور من إشكاليات المناهج في دراسة الأدب العربي القديم في ضوء دراسات أبي العلاء المعري

Author: Muhammad Obaidellah, Published Year: 2018

مؤتمر النقد الأدبي السادس عشر جامعة اليرموك, جامعة اليرموك الاردن

Faculty: Arts

Abstract: تطوّرت "مناهج البحث" في القرون الأخيرة بتأثير من علم المناهج، وبصلة هذا العلم بالفلسفة والمنطق والعلوم، وخلّفت هذه المؤثرات جملة من التوجّهات المنهجية المتمثّلة في الروح العلمية والمنطقية التي ما زالت تسِم منهج البحث حتى اليوم. وتختبر هذه الورقة البحثية مسألة المناهج من خلال الوقوف عند عدد من الدراسات المتعلقة بآثار أبي العلاء المعري (ت449هــ)، وسيكون اهتمامنا منصبّاً على دعواها المنهجية، بهدف معرفة أبرز المناهج التي قُرئ بها المعرّي، وبهدف معاينتها ومراجعة جدواها على المستوى النظري والتطبيقي. وهي المناهج والأمثلة الآتية: أولاً: المنهج التاريخي الطبيعي: ذكرى أبي العلاء لطه حسين ثانيا: اجتهاد في علم النفس الأدبي: رأي في أبي العلاء لأمين الخولي ثالثا: المنهج اللغوي المعجمي: المعري ذلك المجهول لعبد الله العلايلي رابعا: المعري في معركة المنهج والهوية: بين محمود شاكر ولويس عوض: خامساً: المعري في ضوء التفكيك والتأويل: عبد الفتاح كيليطو في متاهات القول المعري مؤلف واحد، لكنّ له صوراً متعددة بتعدّد المناهج والقراءات، كأنما يغدو عدة مؤلفين وليس مؤلفا منفردا، وليس في هذا التعدّد خيانة للمؤلف الواحد، بل لعل فيه إغناء وتوسيعا لمدلولات كلامه الملغّز في وضعه وتصنيفه، وفيه أيضا إغناء للظاهرة المنهجية نفسها. وقد وضعت هذه الدراسات على اختلاف مناهجها أدب المعري في السياق المعاصر، ومرد ذلك إلى نضج تجربة المعري نفسه وتعقدها وتراكبها وصلاحيتها للنظر. وهو أمر يحسب لها، وللمناهج أيضا، بما توفره من إمكانات متنوعة، بصرف النظر عن أية ملاحظ جزئية تتصل بفهم الباحث أو بعض جوانب كفاءته.

Keywords: مناهج النقد، المعري، الأدب العربي القديم

Research Title: Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14

Author: Tawfiq Froukh, Published Year: 2019

Current Molecular Medicine, 19

Faculty: Science

Abstract: Abstract: Background: Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical. Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases. Methods: In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family. The Homozygous frameshift variant NM_001253826.1:c.60delC;p.Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14). The variant does not exist in all public databases neither in our internal exome database. Moreover, no database harbours homozygous loss of function variants in the candidate gene. GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-Dgalactosamine residue to a serine or threonine residue on target proteins especially Mucins. Conclusion: As alterations of mucin’s glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.

Keywords: NGS, genome, ocular, epithelial, dry-eye, keratoconus.

Research Title: Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14

Author: Tawfiq Froukh, Published Year: 2019

Current Molecular Medicine, 19

Faculty: Science

Abstract: Abstract: Background: Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical. Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases. Methods: In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family. The Homozygous frameshift variant NM_001253826.1:c.60delC;p.Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14). The variant does not exist in all public databases neither in our internal exome database. Moreover, no database harbours homozygous loss of function variants in the candidate gene. GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-Dgalactosamine residue to a serine or threonine residue on target proteins especially Mucins. Conclusion: As alterations of mucin’s glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.

Keywords: NGS, genome, ocular, epithelial, dry-eye, keratoconus.

Research Title: Genetic study in a family with dopa-responsive dystonia revealed a novel mutation in sepiapterin reductase gene

Author: Tawfiq Froukh, Published Year: 2019

Pak J Med Sci, 35

Faculty: Science

Abstract: Dopa-responsive dystonia due to sepiapterin reductase deficiency (OMIM#612716) is caused by recessive mutations in the gene encoding sepiapterin reductase (SPR), which plays an important role in the biosynthesis of tetrahydrobiopterin (BH4). One Jordanian patient to first cousin parents is reported in this study. The parents of the proband have recognized the symptoms of their daughter at six months old with motor developmental delay. The symptoms were progressed after-then to include speech delay, seizure, ataxia, oculomotor apraxia, dysarthia and choreoathetosis. Despite of these symptoms, the clinicians in Jordan were unable to diagnose the case. In August 2018, the proband (8 years old) was presented to the department of biotechnology and genetic engineering at Philadelphia University in Jordan for the purposes of performing whole exome sequencing (WES). Analysis of WES data has revealed novel homozygous frameshift variant in the gene SPR (NM_003124.4:c.40delG,p.Ala15Profs*100). The variant is heterozygous in the parents and in the healthy male siblings. Therefore, the studied case was diagnosed with sepiapterin reductase deficiency. Because this disease is likely to be treated recommendations were given to the family immediately to start treatments trials. The case in this study illustrates the difficulties of diagnosing sepiapterin reductase deficiency based on clinical symptoms only and thus renders the possibilities of early management. Also, this study reinforces the importance of running WES to undiagnosed neurodevelopmental cases.

Keywords: Intellectual disability, Serotonin, Dopamine, Autosomal recessive, Genome.

Research Title: First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan

Author: Tawfiq Froukh, Published Year: 2019

BioMed Research International, 2019

Faculty: Science

Abstract: Leukodystrophies (LDs) are heterogeneous genetic disorders characterized by abnormalwhite matter in the central nervous system. Some of the LDs are progressive and often fatal. In general, LD is primarily diagnosed based on the neuroimaging; however, definitive diagnosis of the LD type is done using genetic testing such as next-generation sequencing. The aim of this study is to identify the genetic causes of LD in two independent Jordanian cases that exhibit MRI findings confirming LD with no definitive diagnosis using whole exome sequencing (WES). The most likely causative variants were identified. In one case, the homozygous pathogenic variant NM 000049.2:c.914C>A;p.Ala305Glu, which is previously reported in ClinVar, in the gene ASPA was identified causing Canavan disease. In the second case, the homozygous novel variant NM 000487.5:c.256C>G;p.Arg86Gly in the gene ARSA was identified causing metachromatic leukodystrophy. The two variants segregate in their families. The phenotypes of the two studied cases overlap with assigned diseases. The present study raises the importance of using WES to identify the precise neurodevelopmental diseases in Jordan.

Keywords: epilepsy; heterozygous; IQ; mental retardation; next generation sequencing

Research Title: Two cases of variant late infantile ceroid lipofuscinosis in Jordan

Author: Tawfiq Froukh, Published Year: 2019

World Journal of Clinical Cases, 7

Faculty: Science

Abstract: Abstract BACKGROUND Late infantile ceroid lipofuscinosis is a rare neurodegenerative disorder that appears between the ages of 2 and 4 years and is difficult to diagnose. In this report we present two sisters with this condition, and the clinical course consisted of delayed developmental skills initially and later regression of previously acquired skills. The cases were initially considered as childhood disintegrative disorder (CDD); however, when whole exome sequencing (WES) genetic testing was done, they proved to be variant late infantile ceroid lipofuscinosis. This is the first report from Jordan. CASE SUMMARY Clinical presentation included developmental delay and initially speech delay, followed by lose of sphincter control. Motor development was normal until 4 years of age, then they developed ataxia (fear of going downstairs) and weakness while walking. Atonic and myoclonic seizures become intractable, and this was followed by inability to stand or sit and loss of expressive language. In addition to complete blood count test, liver function test, kidney function test, serum electrolyte test, and blood sugar test, serum amino acid profile, B12 level test, thyroid function test, and a brain computed tomography scan were also normal. An electroencephalogram showed a generalized spike and wave pattern, and magnetic resonance imaging showed little to no abnormalities. After dealing with the cases as CDD, WES testing proved a final diagnosis of variant late infantile ceroid lipofuscinosis. Current treatment is anti-epileptic drugs and supportive care at home, and they are now in vegetative state. CONCLUSION This report highlights the importance of WES for the identification of genetic diseases, especially neurodegenerative disorders.

Keywords: Ceroid lipofuscinosis; Childhood disintegrative disorder; Lysosomal storage disorders; Neurodegenerative disorders; Variant late infantile; Case report

Research Title: Next Generation Sequencing and Genome-Wide Genotyping Identify the Genetic Causes of Intellectual Disability in Ten Consanguineous Families from Jordan

Author: Tawfiq Froukh, Published Year: 2017

Tohoku J. Exp. Med., 243

Faculty: Science

Abstract: Intellectual disability (ID), occurs in approximately 1 to 3% of the population and tends to be higher in low-income countries and in inbred communities. Despite the high rates of consanguineous marriages and the likely enrichment for recessive forms of ID, the genetic bases of ID in Jordan are largely unstudied. In this study, whole exome sequencing (WES) and homozygosity mapping were used to identify the genetic causes of ID in ten families from Jordan. The studied families are characterized by consanguineous marriage and having one or more progeny with ID. Likely disease-causing missense mutations were identified in eight families; four families are due to mutations in genes previously implicated with ID and the other four families are due to mutations in genes that are not previously implicated with ID. The novel genes include: BSN (Protein Basson), PTCHD2 (Protein dispatched homolog 3), DHRS3 (Short-chain dehydrogenase/reductase 3), and LGI3 (Leucine-rich repeat LGI family member 3). In addition, copy number variant (CNV) deletion and/or duplication were identified in 2 families; one family with 3.5 mega base (Mb) deletion on chromosome17 previously implicated with Smith Magenis Syndrome, and the other family with a novel combination of deletion and duplication in chromosomes 5 and 11. In this pilot study, four genes and one CNV deletion/duplication are identified for the first time in association with ID. The finding of this study further demonstrates the power of WES and homozygosity mapping for clinical diagnostics of ID in consanguineous families in small populations.

Keywords: epilepsy; heterozygous; IQ; mental retardation; next generation sequencing

Research Title: Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders

Author: Tawfiq Froukh, Published Year: 2017

JAMAPsychiatry, 74

Faculty: Science

Abstract: IMPORTANCE Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown. OBJECTIVES To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families. DESIGN, SETTING, AND PARTICIPANTS Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID). The study was conducted from July 1, 2008, to June 30, 2015, and data analysis was conducted from July 1, 2015, to August 31, 2016. RESULTS Of the 152 consanguineous families enrolled, 1 child (in 45 families [29.6%]) or multiple children (107 families [70.4%]) had ID; additional features were present in 140 of the families (92.1%). The mean (SD) age of the children was 10.3 (9.0) years, and 171 of 297 (57.6%) were male. In 109 families (71.7%), potentially protein-disrupting and clinically relevant variants were identified. Of these, a clear clinical genetic diagnosis was made in 56 families (36.8%) owing to 57 (likely) pathogenic variants in 50 genes already established in neurodevelopmental disorders (46 autosomal recessive, 2 X-linked, and 2 de novo) or in 7 previously proposed recessive candidates. In 5 of these families, potentially treatable disorders were diagnosed (mutations in PAH, CBS, MTHFR, CYP27A1, and HIBCH), and in 1 family, 2 disease-causing homozygous variants in different genes were identified. In another 48 families (31.6%), 52 convincing recessive variants in candidate genes that were not previously reported in regard to neurodevelopmental disorders were identified. Of these, 14 were homozygous and truncating in GRM7, STX1A, CCAR2, EEF1D, GALNT2, SLC44A1, LRRIQ3, AMZ2, CLMN, SEC23IP, INIP, NARG2, FAM234B, and TRAP1. The diagnostic yield was higher in individuals with severe ID (35 of 77 [45.5%]), in multiplex families (42 of 107 [39.3%]), in patients with additional features (30 of 70 [42.9%]), and in those with remotely related parents (15 of 34 [44.1%]). CONCLUSIONS AND RELEVANCE Because of the high diagnostic yield of 36.8%and the possibility of identifying treatable diseases or the coexistence of several disease-causing variants, using exome sequencing as a first-line diagnostic approach in consanguineous families with neurodevelopmental disorders is recommended. Furthermore, the literature is enriched with 52 convincing candidate genes that are awaiting confirmation in independent families.

Keywords: ID, NGS, WES

Research Title: Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features

Author: Tawfiq Froukh, Published Year: 2016

The American Journal of Human Genetics, 99

Faculty: Science

Abstract: The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysophosphatidylinositol acyltransferase (LPIAT1). Subjects presented with ID frequently accompanied by epilepsy and autistic features. LPIAT1 is a membrane-bound phospholipid-remodeling enzyme that transfers arachidonic acid (AA) to lysophosphatidylinositol to produce AA-containing phosphatidylinositol. This study suggests a role for AA-containing phosphatidylinositols in the development of ID accompanied by epilepsy and autistic features.

Keywords: ID, NGS, WES