Genetic Disorders in Sudan

Salih, Mustafa A.

doi:10.1007/978-3-642-05080-0_20

Cited by 8 publications

(4 citation statements)

References 123 publications

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“…23 Relatively little is known about the genetics of spinocerebellar degenerations in the Sudanese population. 24 In this article, we studied 25 families with progressive spastic neurodegenerative disorders in an effort to determine the genes underlying the disease. We report the first seven Sudanese families carrying novel and rare variants in KIAA1840 (SPG11), TFG/SPG57, ATL1 (SPG3A), ALS2 and SACS.…”

Section: Introductionmentioning

confidence: 99%

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

et al. 2016

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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 HSPrelated 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.

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Section: Introductionmentioning

confidence: 99%

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

et al. 2016

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“…The importance of medical genetics and its vital role in paediatric practice have been acknowledged by the pioneer paediatricians in Sudan. The Late Professor Mahmoud Mohamed Hassan [3], the first qualified Sudanese paediatrician, was the first Sudanese doctor to obtain a post graduate MD from the University of Khartoum (U of K) more than 50 years ago (1965) with a thesis on "Genetic Diseases in Sudanese Children" [4]. Using his clinical skills and basic laboratory investigations, he managed to describe several genetic disorders for the first time in Africa and Arab Region, including Down syndrome, haemoglobinopathies, Hartnup disease, phenylketonuria and vitamin D dependent type 2 rickets.…”

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confidence: 99%

“…His report on Down syndrome [5] was published 3 years before the identification of trisomy 21 as the cause of Down syndrome by Lejeune et al [6]. His delineation of a Sudanese family with five children who had vitamin D dependent type 2 rickets came 1 year before the first description of the disease worldwide [4]. Professor Mohamed Ibrahim A. Omer [7], the first Convenor of Postgraduate Board of Paediatrics and later the Director of Postgraduate Medical Studies Board, was also visionary in establishing a curriculum on medical genetics for the local specialty training in paediatrics.…”

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confidence: 99%

The odyssey of diagnosing genetic disorders in evolving health services

Salih¹,

Swar²

2019

Sudan J Paed

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“…This disease is unusually frequent in Slovakia and the Dominican Republic (Milch, 1960;O'Brien et al, 1963). HGA excretion ranges from 1 to 8 g daily in the urine (Khachadurian & Abu Feisal, 1958;Salih, 1997). In urine, as in tissues, HGA oxidises to benzoquinone acetic acid, which in turn forms HGA-melanin-based polymers (Martin Jr & Batkoff, 1987), deposited in the connective tissue, most commonly the joints, cardiovascular system, kidney and skin (Helliwell et al, 2008), causing a pigmentation known as "ochronosis."…”

Section: Introductionmentioning

confidence: 99%

Mutation Screening of theHGDGene Identifies a Novel Alkaptonuria Mutation with Significant Founder Effect and High Prevalence

Sakthivel

Zaťková

Nemethova

et al. 2014

Annals of Human Genetics

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SummaryAlkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2-dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU-causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin.

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Genetic Disorders in Sudan

Cited by 8 publications

References 123 publications

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

The odyssey of diagnosing genetic disorders in evolving health services

Mutation Screening of theHGDGene Identifies a Novel Alkaptonuria Mutation with Significant Founder Effect and High Prevalence

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