Salia Bamba ^1,2 Lala N. Sidibé ³ Seybou H. Diallo ^1,4 Lassana Cissé ¹ Kékouta Dembélé ⁵ Abdoulaye Yalcouye ¹ Weizhen Ji ² Mohamed E. Dembélé ¹ Salimata Diarra ^1,2 Alassane Dit Baneye Maiga ¹ Oumou Traoré ¹ Salimata Diallo ⁴ Samuel E. Mefoung ¹ Amadou Touré ^3,5 Adama Koné ⁵ Lauren Jeffries ² Oumar Guinto ^1,6 Emily K. Mis ² Kenneth Fischbeck ⁷ Mustafa Khokha ² Saquib A. Lakhani ² Guida Landouré ^1,6*

• ¹ Faculté de Médecine et d'Odontostomatologie, Université des Sciences, des Techniques et des Technologies de Bamako, Bamako, Mali
• ² Department of Pediatrics, School of Medicine, Yale University, New Haven, United States
• ³ Service de Pédiatrie, Centre Hospitalier Universitaire de Gabriel Touré, Bamako, Mali
• ⁴ Service de Neurologie, Centre Hospitalier Universitaire de Gabriel Touré, Bamako, Mali
• ⁵ Independent researcher, Bamako, Mali
• ⁶ Service de Neurologie, Centre Hospitalier Universitaire du Point G, Bamako, Mali
• ⁷ National Institute of Neurological Disorders and Stroke (NIH), Bethesda, United States

Developmental and epileptic encephalopathies (DEEs) are a group of neurological disorders characterized by early-onset seizures that are often resistant to treatment, by electroencephalographic abnormalities, and by developmental delay or regression. Their genetic basis remains largely unelucidated, especially in sub-Saharan Africa (SSA). We investigated the genetic bases of DEE in three Malian families.Patients underwent clinical evaluation, and DNA was obtained for whole exome sequencing (WES). Putative variants were screened in all available family members and in silico prediction analyses were performed to assess pathogenicity.Five patients from three unrelated families with DEEs had symptoms that started during the neonatal period with seizures and myoclonus that became refractory to antiepileptic medications. WES identified previously unreported variants in all three families: homozygous variants in GRIN1 and SYNJ1, and compound heterozygous variants in RARS2. These variants affected protein structure by in silico tools and were classified as variants of uncertain significance hot , pathogenic/likely pathogenic respectively according to ACMG criteria.We identified rare variants in three genes (GRIN1, SYNJ1, and RARS2) associated with early onset of DEEs in SSA, expanding their genetic and epidemiological spectrum. Larger cohort studies in SSA may unravel more variants with potential clinical implications and further our understanding of the disease mechanism.