Al-Ajmi A, Shamsah S, Janicijevic A, Williams M, Al-Mulla F. Novel frameshift mutation in the SACS gene causing spastic ataxia of charlevoix-saguenay in a consanguineous family from the Arabian Peninsula: A case report and review of literature. World J Clin Cases 2020; 8(8): 1477-1488 [PMID: 32368540 DOI: 10.12998/wjcc.v8.i8.1477]
Corresponding Author of This Article
Fahd Al-Mulla, FRCPE, MBChB, PhD, Full Professor, Director, Department of Genetics, Genatak Center for Genomic Medicine, Mirqab, Kuwait City 12000, Kuwait. fahd@al-mulla.org
Research Domain of This Article
Clinical Neurology
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. Apr 26, 2020; 8(8): 1477-1488 Published online Apr 26, 2020. doi: 10.12998/wjcc.v8.i8.1477
Novel frameshift mutation in the SACS gene causing spastic ataxia of charlevoix-saguenay in a consanguineous family from the Arabian Peninsula: A case report and review of literature
Abdullah Al-Ajmi, Sarah Shamsah, Aleksandar Janicijevic, Michayla Williams, Fahd Al-Mulla
Abdullah Al-Ajmi, Neurology Unit, Al-Jahra Hospital, Jahra City 13110, Kuwait
Sarah Shamsah, Faculty of Allied Health Sciences, Kuwait University, Kuwait City 13110, Kuwait
Aleksandar Janicijevic, Department of Radiology, Al-Jahra Hospital, Jahra City 13110, Kuwait
Michayla Williams, Fahd Al-Mulla, Department of Genetics, Genatak Center for Genomic Medicine, Kuwait City 12000, Kuwait
Author contributions: Al-Ajmi A performed the physical examination, clinical assessment and EDX, collected clinical and workup data, and drafted the manuscript for intellectual content; Shamsah S interpreted the data and revised the manuscript for intellectual content; Janicijevic A performed and interpreted the radiological data and revised the manuscript for intellectual content; Williams M performed the genetic study and revised the manuscript for intellectual content; Al-Mulla F counseled the family designed, collected and analyzed NGS data, reviewed the literature, and drafted the manuscript. All authors issued final approval for the version to be submitted.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declared that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the curve checklist 2016 and the manuscript was prepared and revised according to the care checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Fahd Al-Mulla, FRCPE, MBChB, PhD, Full Professor, Director, Department of Genetics, Genatak Center for Genomic Medicine, Mirqab, Kuwait City 12000, Kuwait. fahd@al-mulla.org
Received: December 17, 2019 Peer-review started: December 17, 2019 First decision: April 1, 2020 Revised: April 10, 2020 Accepted: April 18, 2020 Article in press: April 18, 2020 Published online: April 26, 2020 Processing time: 122 Days and 18.4 Hours
Abstract
BACKGROUND
Familial cases of autosomal recessive spastic ataxia of charlevoix-saguenay have not been reported in the Arabian Peninsula, although the consanguineous marriage rate is very high. We report the first family from the Arabian Peninsula harboring a novel frameshift mutation in the SACS gene.
CASE SUMMARY
A 33-year-old man presented to our neurology clinic with balance problems and weakness of distal upper and lower limbs. He was previously clinically diagnosed with Friedreich's ataxia. However, the severity of polyneuropathy and the electrodiagnostic studies (EDX) findings are atypical features of Friedreich’s ataxia, and the deterioration was attributed to diabetic neuropathy. Close examination of other family members identified cerebellar ataxia, lower-limb pyramidal signs, peripheral neuropathy, and magnetic resonance imaging findings characterized by pontine linear hypointensities. Genetic testing for Friedreich’s ataxia did not yield a diagnosis. Whole exome sequencing identified a novel frameshift germline mutation in the SACS gene termed c.5824_5827delTACT using the transcript NM_014363.5, which is predicted to cause premature termination of the sacsin protein at amino acid position 1942 (p.Tyr1942Metfs*9) and disrupts the sacsin SRR3 and domains downstream from it. The mutation segregated with the disease in the family.
CONCLUSION
Our data add to the spectrum of mutations in the SACS gene and argues for a need to implement suitably integrated clinical and diagnostic services, including next generation sequencing technology, to better classify ataxia in this area of the world.
Core tip: Autosomal recessive spastic ataxia of charlevoix-saguenay has not been reported previously in the Arabian peninsula where the consanguinity rate is high. We present herein, the first family with autosomal recessive spastic ataxia of charlevoix-saguenay harboring a novel SACS gene frameshift pathogenic mutation and argue that the disease may be underdiagnosed due to the lack of proper laboratory-clinical integration. This case highlights the importance of integrating the next generation sequencing pipeline for optimal diagnosis of neurological disorders.
