Browsing by Author "Elbashir,Mustafa I"

Now showing 1 - 3 of 3

Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family
(BMC Medical Genetics, 2018) Elsayed,Liena E. O; Mohammed,Inaam N; Hamed,Ahlam A. A; Elseed,Maha A; Salih,Mustafa A. M; Yahia,Ashraf; Siddig,Rayan A; Amin,Mutaz; Koko,Mahmoud; Elbashir,Mustafa I; Ibrahim,Muntaser E; Brice,Alexis; Ahmed,Ammar E; Stevanin,Giovanni
Background: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent. Case presentation: Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found in PLA2G6. It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members. Conclusion: This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients’ phenotype). Therefore this variant can be currently annotated as “pathogenic”. This is the first study to report mutations in PLA2G6 gene in patients from Sudan.
Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan
(European Journal of Human Genetics, 2016) Elsayed,Liena EO; Mohammed,Inaam N; Hamed,Ahlam AA; Elseed,Maha A; Johnson,Adam; Mairey,Mathilde; Mohamed,Hassab Elrasoul SA; Idris,Mohamed N; Salih,Mustafa AM; El-sadig,Sarah M; Koko,Mahmoud E; Mohamed,Ashraf YO; Raymond,Laure; Coutelier,Marie; Darios,Frédéric; Siddig,Rayan A; Ahmed,Ahmed KMA; Babai,Arwa MA; Malik,Hiba MO; Omer,Zulfa MBM; Mohamed,Eman OE; Eltahir,Hanan B; Magboul,Nasr Aldin A; Bushara,Elfatih E; Elnour,Abdelrahman; Rahim,Salah M Abdel; Alattaya,Abdelmoneim; Elbashir,Mustafa I; E Ibrahim,Muntaser; Durr,Alexandra; Audhya,Anjon; Brice,Alexis; Ahmed,Ammar E; Stevanin,Giovanni
Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP- related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C4T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C4T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.
In transition: current health challenges and priorities in Sudan
(BMJ Global Health, 2019) Charani,Esmita; Cunnington,Aubrey J; Yousif,AlaEldin H A; Ahmed,Mohammed Seed; Ahmed,Ammar E M; Babiker,Souad; Badri,Shahinaz; Buytaert,Wouter; Crawford,Michael A; Elbashir,Mustafa I; Elhag,Kamal; Elsiddig,Kamal E; Hakim,Nadey; Johnson,Mark R; Miras,Alexander D; Swar,Mohamed O; Templeton,Michael R; Taylor-Robinson,Simon David
A recent symposium and workshop in Khartoum, the capital of the Republic of Sudan, brought together broad expertise from three universities to address the current burden of communicable and non-communicable diseases facing the Sudanese healthcare system. These meetings identified common challenges that impact the burden of diseases in the country, most notably gaps in data and infrastructure which are essential to inform and deliver effective interventions. Non-communicable diseases, including obesity, type 2 diabetes, renal disease and cancer are increasing dramatically, contributing to multimorbidity. At the same time, progress against communicable diseases has been slow, and the burden of chronic and endemic infections remains considerable, with parasitic diseases (such as malaria, leishmaniasis and schistosomiasis) causing substantial morbidity and mortality. Antimicrobial resistance has become a major threat throughout the healthcare system, with an emerging impact on maternal, neonatal and paediatric populations. Meanwhile, malnutrition, micronutrient deficiency and poor perinatal outcomes remain common and contribute to a lifelong burden of disease. These challenges echo the United Nations (UN) sustainable development goals and concentrating on them in a unified strategy will be necessary to address the national burden of disease. At a time when the country is going through societal and political transition, we draw focus on the country and the need for resolution of its healthcare needs.