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.

Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 affected patients from 38 unrelated Sudanese families segregating multiple forms of SCDs. The age-at-onset in our cohort ranged from birth to 35 years; however, most patients manifested childhood-onset diseases (the mean and median ages at onset were 7.5 and 3 years, respectively). We reached the genetic diagnosis in 63% and possibly up to 73% of the studied families when considering variants of unknown significance. Combining the present data with our previous analysis of 25 Sudanese HSP families, the success rate reached 52–59% (31–35/59 families). In this article we report candidate variants in genes previously known to be associated with SCDs or other phenotypically related monogenic disorders. We also highlight the genetic and clinical heterogeneity of SCDs in Sudan, as we did not identify a major causative gene in our cohort, and the potential for discovering novel SCD genes in this population.

Hereditary spinocerebellar degenerative disorders (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include spastic paraplegia, spastic ataxia, cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 patients from 38 unrelated Sudanese families segregating multiple forms of SCDs focusing on known human disease-associated genes. We reached the genetic diagnosis in 63% and up to 73% of the studied families when considering variants of unknown significance. Taking into account a series of Sudanese families that we previously analyzed, the combined success rate in the two series reached 52–59% (31–35/59 families). We also highlighted the genetic and clinical heterogeneity of SCDs in Sudan, as we identified no single major gene in our cohort and the potential for discovering novel SCDs genes in this population.

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Introduction:This study aims to compare the binaural interaction component of auditory brainstem response (ABR-BIC) between children with stuttering and normal peers, and to correlate ABR-BIC parameters with stuttering severity instrument -3. Patients and Methods: Twenty Stuttering children, diagnosed according to the criteria of stuttering severity instrument -3, and 20 normal age and gender matched peers were included. Click evoked ABRs were recorded through right monaural, left monaural and binaural stimulation at 80 dBnHL in both study groups. ABR-BIC was calculated as the difference between the binaurally evoked ABR response and the algebraic sum of the left and right monaural responses, and ABR-BIC parameters were measured. Results: ABR-BIC latency and duration were significantly prolonged in the stuttering group compared to the control group, while ABR-BIC amplitude and area under the curve (AUC) were comparable. Also, ABR-BIC amplitude and AUC were significantly correlated with stuttering severity. Conclusion:The results of this study point to impaired timing and reduced overall magnitude of binaural interaction at the brainstem level in stuttering children.