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 Children’s Hospital NHS Foundation Trust, Sheffield, United Kingdom

Josh Willoughby

Sheffield Diagnostic Genetic Service, Sheffield Children’s 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