EJMCR. 2020; 4(4): 110-115

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.

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


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Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings


Authors
Min Tsui Ong
Paediatric Neurology, Sheffield Children’s Hospital NHS Foundation Trust, Sheffield, United Kingdom
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Josh Willoughby
Sheffield Diagnostic Genetic Service, Sheffield Children’s Hospital NHS Foundation Trust, Sheffield, United Kingdom
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Daniel J A Connolly
Neuroradiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
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Santosh Mordekar
Paediatric Neurology, Sheffield Children’s Hospital NHS Foundation Trust, Sheffield, United Kingdom
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D D D Study
Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
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Diana Johnson
Clinical Genetics, Sheffield Children’s Hospital NHS Foundation Trust, Sheffield, United Kingdom
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Correspondence to:
. Min Tsui Ong, Paediatric Neurology, Sheffield Children’s Hospital NHS Foundation Trust, Ryegate Children’s Centre, Sheffield, United Kingdom.; mintsui.ong@gmail.com

Publication history
Received 26 Feb 2019
Revised 17 Mar 2020
Accepted 01 Apr 2020
Published online 10 Apr 2020
Published in print 24 May 2020

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Pubmed Style

Ong MT, Willoughby J, Connolly DJA, Mordekar S, Study DDD, Johnson D. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR. 2020; 4(4): 110-115. doi:10.24911/ejmcr/1731551044010


Web Style

Ong MT, Willoughby J, Connolly DJA, Mordekar S, Study DDD, Johnson D. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. https://www.ejmcr.com/?mno=33365 [Access: July 11, 2020]. doi:10.24911/ejmcr/1731551044010


AMA (American Medical Association) Style

Ong MT, Willoughby J, Connolly DJA, Mordekar S, Study DDD, Johnson D. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR. 2020; 4(4): 110-115. doi:10.24911/ejmcr/1731551044010


Vancouver/ICMJE Style

Ong MT, Willoughby J, Connolly DJA, Mordekar S, Study DDD, Johnson D. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR. (2020), [cited July 11, 2020]; 4(4): 110-115. doi:10.24911/ejmcr/1731551044010


Harvard Style

Ong, M. T., Willoughby, . J., Connolly, . D. J. A., Mordekar, . S., Study, . D. D. D. & Johnson, . D. (2020) Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. EJMCR, 4 (4), 110-115. doi:10.24911/ejmcr/1731551044010


Turabian Style

Ong, Min Tsui, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, and Diana Johnson. 2020. Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. European Journal of Medical Case Reports, 4 (4), 110-115. doi:10.24911/ejmcr/1731551044010


Chicago Style

Ong, Min Tsui, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, and Diana Johnson. "Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings." European Journal of Medical Case Reports 4 (2020), 110-115. doi:10.24911/ejmcr/1731551044010


MLA (The Modern Language Association) Style

Ong, Min Tsui, Josh Willoughby, Daniel J. A. Connolly, Santosh Mordekar, D. D. D. Study, and Diana Johnson. "Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings." European Journal of Medical Case Reports 4.4 (2020), 110-115. Print. doi:10.24911/ejmcr/1731551044010


APA (American Psychological Association) Style

Ong, M. T., Willoughby, . J., Connolly, . D. J. A., Mordekar, . S., Study, . D. D. D. & Johnson, . D. (2020) Genotype-phenotype variability of DARS mutation - case reports of a trio of siblings. European Journal of Medical Case Reports, 4 (4), 110-115. doi:10.24911/ejmcr/1731551044010


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