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Novel variants causing megalencephalic leukodystrophy in Sudanese families

Amin, Mutaz ; Vignal, Cedric ; Hamed, Ahlam A.A. ; Mohammed, Inaam N. ; Elseed, Maha A. ; Drunat, Severine ; Babai, Arwa ; Eltaraifee, Esraa ; Elbadi, Iman and Abubaker, Rayan , et al. (2022) In Journal of Human Genetics 67(3). p.127-132
Abstract

Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families. Mutations were screened using the NGS panel testing 139 leukodystrophies and leukoencephalopathies causing genes (NextSeq500 Illumina). Five homozygous MLC1 variants were discovered in seven patients from five distinct families, including three consanguineous families from the same region of Sudan. Three variants were missense (c.971 T > G, p.Ile324Ser;... (More)

Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families. Mutations were screened using the NGS panel testing 139 leukodystrophies and leukoencephalopathies causing genes (NextSeq500 Illumina). Five homozygous MLC1 variants were discovered in seven patients from five distinct families, including three consanguineous families from the same region of Sudan. Three variants were missense (c.971 T > G, p.Ile324Ser; c.344 T > C, p.Phe115Ser; and c.881 C > T, p.Pro294Leu), one duplication (c.831_838dupATATCTGT, p.Ser280Tyrfs*8), and one synonymous/splicing-site mutation (c.762 C > T, p.Ser254). The segregation pattern was consistent with autosomal recessive inheritance. The clinical presentation and brain MRI of the seven affected patients were consistent with the diagnosis of MLC1. Due to the high frequency of distinct MLC1 mutations found in our leukodystrophic Sudanese families, we analyzed the coding sequence of MLC1 gene in 124 individuals from the Sudanese genome project in comparison with the 1000-genome project. We found that Sudan has the highest proportion of deleterious variants in MLC1 gene compared with other populations from the 1000-genome project.

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publishing date
type
Contribution to journal
publication status
published
in
Journal of Human Genetics
volume
67
issue
3
pages
127 - 132
publisher
Springer Nature
external identifiers
  • pmid:34504271
  • scopus:85114601388
ISSN
1434-5161
DOI
10.1038/s10038-021-00945-7
language
English
LU publication?
no
additional info
Publisher Copyright: © 2021, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
id
1e77a0cd-97a1-47f0-96c5-6638f8c6ecb9
date added to LUP
2026-06-05 10:38:46
date last changed
2026-06-06 03:34:13
@article{1e77a0cd-97a1-47f0-96c5-6638f8c6ecb9,
  abstract     = {{<p>Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families. Mutations were screened using the NGS panel testing 139 leukodystrophies and leukoencephalopathies causing genes (NextSeq500 Illumina). Five homozygous MLC1 variants were discovered in seven patients from five distinct families, including three consanguineous families from the same region of Sudan. Three variants were missense (c.971 T &gt; G, p.Ile324Ser; c.344 T &gt; C, p.Phe115Ser; and c.881 C &gt; T, p.Pro294Leu), one duplication (c.831_838dupATATCTGT, p.Ser280Tyrfs*8), and one synonymous/splicing-site mutation (c.762 C &gt; T, p.Ser254). The segregation pattern was consistent with autosomal recessive inheritance. The clinical presentation and brain MRI of the seven affected patients were consistent with the diagnosis of MLC1. Due to the high frequency of distinct MLC1 mutations found in our leukodystrophic Sudanese families, we analyzed the coding sequence of MLC1 gene in 124 individuals from the Sudanese genome project in comparison with the 1000-genome project. We found that Sudan has the highest proportion of deleterious variants in MLC1 gene compared with other populations from the 1000-genome project.</p>}},
  author       = {{Amin, Mutaz and Vignal, Cedric and Hamed, Ahlam A.A. and Mohammed, Inaam N. and Elseed, Maha A. and Drunat, Severine and Babai, Arwa and Eltaraifee, Esraa and Elbadi, Iman and Abubaker, Rayan and Mustafa, Doaa and Yahia, Ashraf and Koko, Mahmoud and Osman, Melka and Bakhit, Yousuf and Elshafea, Azza and Alsiddig, Mohamed and Haroun, Sahwah and Lelay, Gurvan and Elsayed, Liena E.O. and Ahmed, Ammar E. and Boespflug-Tanguy, Odile and Dorboz, Imen}},
  issn         = {{1434-5161}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{127--132}},
  publisher    = {{Springer Nature}},
  series       = {{Journal of Human Genetics}},
  title        = {{Novel variants causing megalencephalic leukodystrophy in Sudanese families}},
  url          = {{http://dx.doi.org/10.1038/s10038-021-00945-7}},
  doi          = {{10.1038/s10038-021-00945-7}},
  volume       = {{67}},
  year         = {{2022}},
}