Case Report
Volume: 4 | Issue: 4 | Published: Apr 10, 2020 | Pages: 110 - 115 | DOI: 10.24911/ejmcr/1731551044010
Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings
Authors: Min Tsui Ong , Josh Willoughby , Daniel J. A. Connolly , Santosh Mordekar , D. D. D. Study , Diana Johnson
Article Info
Authors
Min Tsui Ong
Paediatric Neurology, Sheffield Childrens Hospital NHS Foundation Trust, Sheffield, United Kingdom
Josh Willoughby
Sheffield Diagnostic Genetic Service, Sheffield Childrens Hospital NHS Foundation Trust, Sheffield, United Kingdom
Daniel J. A. Connolly
Neuroradiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
Santosh Mordekar
Paediatric Neurology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom
D. D. D. Study
Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
Diana Johnson
Clinical Genetics, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom
Publication History
Received: February 26, 2019
Revised: March 17, 2020
Accepted: April 01, 2020
Published: April 10, 2020
Abstract
Background: We describe a family with hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), a rare genetic condition causing motor impairment. Case Presentation: Whole exome sequencing (DDD study) was performed on the proband who presented with motor symptoms. Sanger sequencing was done on the proband and two affected siblings to validate the result and confirm segregation of the variant with the phenotype. The phenotype and magnetic resonance imaging pattern of the siblings were compared. The index case and her two affected siblings were found to have the same compound heterozygous mutations in the DARS gene. The siblings had milder presentation than previously reported cases, continuing to walk unsupported and have not developed overt spasticity, but have mild upper motor neuron and cerebellar signs. Clinical severity and imaging findings were variable in this family. Conclusion: We demonstrated intra-familial variability and very mild symptoms in our family with DARS-associated HBSL, widening the phenotypic spectrum of the condition. It is likely that other factors, genetic and environmental, play a role in this variability.
Keywords: DARS gene, hypomyelination, aminoacyl-tRNA synthethase, green
Pubmed Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR. 2020; 10 (April 2020): 110-115. doi:10.24911/ejmcr/1731551044010
Web Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. https://ejmcr.com/articles/1434 [Access: December 25, 2024]. doi:10.24911/ejmcr/1731551044010
AMA (American Medical Association) Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR. 2020; 10 (April 2020): 110-115. doi:10.24911/ejmcr/1731551044010
Vancouver/ICMJE Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR. (2020), [cited December 25, 2024]; 10 (April 2020): 110-115. doi:10.24911/ejmcr/1731551044010
Harvard Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson (2020) Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR, 10 (April 2020): 110-115. doi:10.24911/ejmcr/1731551044010
Chicago Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson. "Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings." 10 (2020), 110-115. doi:10.24911/ejmcr/1731551044010
MLA (The Modern Language Association) Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson. "Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings." 10.April 2020 (2020), 110-115. Print. doi:10.24911/ejmcr/1731551044010
APA (American Psychological Association) Style
Min Tsui Ong, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, Diana Johnson (2020) Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. , 10 (April 2020), 110-115. doi:10.24911/ejmcr/1731551044010