Journal Article

Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report

Abubakr, Rayan, Idris, Razaz, Brice, Alexis, Ahmed, Ammar Eltahir, Salih, Mustafa A., Amin, Mutaz, Babai, Arwa, El-Sadig, Sarah Misbah, Elmalik, Salah A., Yahia, Ashraf, Taha, Shaimaa Omer M.A., Elsayed, Liena, Stevanin, Giovanni, Koko, Mahmoud

2018

Overview

Background Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL, OMIM #611105) is a genetic disease of the central nervous system characterized by lower limb spasticity, cerebellar ataxia and involvement of the dorsal column. The disease is caused by mutations in the DARS2 gene but has never been reported in sub-Saharan Africa so far. Case presentation Two siblings, aged 18 years and 15 years, from a consanguineous family presented with pyramidal signs and symptoms since infancy and developmental delay. Whole exome sequencing of the proband identified two compound heterozygous variants (NM_018122.4:c.1762C > G and c.563G > A) in DARS2 . Sanger sequencing confirmed the presence of the mutations and their segregation in trans in both patients and in their elder sister (aged 20 years), who showed only brisk reflexes and mild lower limb spasticity. Surprisingly, in contrast to her subtle clinical presentation, the elder sister had abnormal MRI features and serum lactate levels comparable to her ill sisters. Conclusion This report illustrates intra-familial phenotypic variation in LBSL and provides an example of a marked dissociation between the clinical and radiological phenotypes of the disease. This may have implications for the detection of mutation carriers in LBSL.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adolescent / Africa / Age / Aspartate-tRNA Ligase - genetics / Ataxia / Brain stem / Case Report / Case reports / Central nervous system / Cerebellar ataxia / Cerebellum / Clinico-radiological dissociation / Convulsions & seizures / DARS2 / Female / Genetic aspects / Genetic disorders / Genetics / Health aspects / Human genetics / Humans / Intra-familial phenotypic heterogeneity / Lactic acid / LBSL / Leukoencephalopathies - genetics / Leukoencephalopathy / Life Sciences / Magnetic resonance imaging / Medicine / Medicine & Public Health / Mutation / Nervous system / Neurobiology / Neurochemistry / Neurogenetics / Neurology / Neurons and Cognition / Neurosurgery / NMR / Nuclear magnetic resonance / Patients / Pedigree / Phenotype / Phenotypes / Phenotypic variations / Reflexes / Siblings / Spasticity / Spinal cord / Sudan / Young Adult