Novel variants causing inherited leukodystrophies

Novel variants causing inherited leukodystrophies

Novel variants causing inherited leukodystrophies in Sudanese families

Mutaz Amin1, Imen Dorboz2, Inaam N. Mohammed1, Ahlam A. A. Hamed1, Maha A. Elseed1, Ashraf Yahia1, Arwa Babai1, Eman Badi1, Melka O. EL-Amin1, Esraa Emad1, Simon Samaan2,3, Liena E. O. Elsayed1, Ammar E. Ahmed1* and Odile Boespflug-Tanguy2,4*

*Correspondence: Professor Ammar E. Ahmed: Faculty of Medicine, University of Khartoum, Qasr Street,11111 Khartoum, Sudan and Professor Odile Boespflug-Tanguy: INSERM 1141 Neuropediatrics and metabolic disorders unit, Hospital Robert Debre, Paris, France

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1Faculty of Medicine, University of Khartoum, Sudan

2INSERM UMR 1141 PROTECT,  Université Paris Diderot- Sorbonne Paris Cité, France 

3Medical Genetic Department, Molecular Genetic unit, CHU APHP , Robert-Debré  Paris, France 

4Neuropediatrics and Metabolic Disorders Department, reference center for leukodystrophies and rare leukoencéphalopathies (LEUKOFRANCE), CHU APHP Robert-Debré, Paris, France


Background: Leukodystrophies are a group of inherited disorders primarily affecting the white matter of the CNS. There are currently 30 recognized forms of leukodystrophies with distinct clinical, biochemical and radiological characteristics. However, the genetics of these classical forms of leukodystrophies remain unknown in many parts of the world especially in Sub-Saharan Africa.

Methods: In this study, we selected 5 consanguineous leukodystrophic families from Sudan using clinical and MRI recognition pattern. Genomic DNA was extracted and screened for mutations using NGS panel testing 153 leukodystrophies and leucoencephalopathies causing genes (NextSeq500 Illumina).

Results: Three novel homozygous variants were discovered: one (c.380G>C, p.Arg127Pro) in PSAP gene causing MLD, and two (c.831_838DUPATATCTGT, p.Ser280Tyrfs*8 and c.971T>G, p.Ile324Ser) in MLC1 gene in the two families with MLC. The segregation pattern was consistent with autosomal recessive inheritance. The pathogenicity of these variants was predicted using bioinformatics tools.

Conclusion: This is the first study to underlie the genetics of leukodystrophies in Sudan. Analysis of additional families are in progress in order to establish the whole spectrum of genetic variations causing inherited leukodystrophies in Sudanese families.


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