Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report
Abstract 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 mu...
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doaj-ae4df711b5b34bab82c19856123ad5dc2020-11-25T01:42:21ZengBMCBMC Neurology1471-23772018-10-011811610.1186/s12883-018-1180-7Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case reportAshraf Yahia0Liena Elsayed1Arwa Babai2Mustafa A. Salih3Sarah Misbah El-Sadig4Mutaz Amin5Mahmoud Koko6Rayan Abubakr7Razaz Idris8Shaimaa Omer M.A. Taha9Salah A. Elmalik10Alexis Brice11Ammar Eltahir Ahmed12Giovanni Stevanin13Department of Biochemistry, Faculty of Medicine, University of KhartoumDepartment of Biochemistry, Faculty of Medicine, University of KhartoumInstitute of Endemic Diseases, University of KhartoumDivision of Pediatric Neurology, Department of Pediatrics, College of Medicine, King Saud UniversityDepartment of Medicine, Faculty of Medicine, University of KhartoumDepartment of Biochemistry, Faculty of Medicine, University of KhartoumDepartment of Neurology & Epileptology, Hertie Institute for Clinical Brain Research, University of TübingenInstitute of Endemic Diseases, University of KhartoumInstitute of Endemic Diseases, University of KhartoumDepartment of Radiology, Dar Al Elaj specialized hospitalDepartment of Physiology, College of Medicine, King Saud UniversityDepartment of Genetics, APHP, Pitié-Salpêtrière HospitalDepartment of Physiology, Faculty of Medicine, University of KhartoumEcole Pratique des Hautes Etudes, EPHE, PSL Research UniversityAbstract 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.http://link.springer.com/article/10.1186/s12883-018-1180-7LBSLDARS2Clinico-radiological dissociationIntra-familial phenotypic heterogeneityAfrica |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ashraf Yahia Liena Elsayed Arwa Babai Mustafa A. Salih Sarah Misbah El-Sadig Mutaz Amin Mahmoud Koko Rayan Abubakr Razaz Idris Shaimaa Omer M.A. Taha Salah A. Elmalik Alexis Brice Ammar Eltahir Ahmed Giovanni Stevanin |
spellingShingle |
Ashraf Yahia Liena Elsayed Arwa Babai Mustafa A. Salih Sarah Misbah El-Sadig Mutaz Amin Mahmoud Koko Rayan Abubakr Razaz Idris Shaimaa Omer M.A. Taha Salah A. Elmalik Alexis Brice Ammar Eltahir Ahmed Giovanni Stevanin Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report BMC Neurology LBSL DARS2 Clinico-radiological dissociation Intra-familial phenotypic heterogeneity Africa |
author_facet |
Ashraf Yahia Liena Elsayed Arwa Babai Mustafa A. Salih Sarah Misbah El-Sadig Mutaz Amin Mahmoud Koko Rayan Abubakr Razaz Idris Shaimaa Omer M.A. Taha Salah A. Elmalik Alexis Brice Ammar Eltahir Ahmed Giovanni Stevanin |
author_sort |
Ashraf Yahia |
title |
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report |
title_short |
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report |
title_full |
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report |
title_fullStr |
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report |
title_full_unstemmed |
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report |
title_sort |
intra-familial phenotypic heterogeneity in a sudanese family with dars2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report |
publisher |
BMC |
series |
BMC Neurology |
issn |
1471-2377 |
publishDate |
2018-10-01 |
description |
Abstract 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. |
topic |
LBSL DARS2 Clinico-radiological dissociation Intra-familial phenotypic heterogeneity Africa |
url |
http://link.springer.com/article/10.1186/s12883-018-1180-7 |
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