A Novel Variant in CWF19L1 Gene in a Family with Late-Onset Autosomal Recessive Cerebellar Ataxia 17

ABSTRACT

Introduction

Previously published studies demonstrated that mutations in CWF19L1 cause early-onset autosomal recessive cerebellar ataxia 17. In this article, we report a novel homozygous missense variant in CWF19L1 in two sisters who had late-onset cerebellar ataxia with epilepsy and describe their clinical and neuroradiological findings.

Methods

We included two female patients with typical symptoms of cerebellar ataxia supported by the MRI findings. Whole exome sequencing (WES) data analysis was performed to identify the underlying genetic defect in the proband. Sanger sequencing was used to confirm the variant in other family members.

Results

WES revealed a homozygous missense variant in CWF19-like protein 1; CWF19L1 gene c.395A>G; p.(Asp132Gly) (RefSeq NM_018294.4). This variant has not been described previously in the literature. Mutations in this gene are known to cause an autosomal recessive disorder, spinocerebellar ataxia, autosomal recessive 17 (OMIM #616127).

Conclusion

In conclusion, we report a novel variant in CWF19L1 as a candidate causal variant in two sisters with autosomal recessive cerebellar ataxia. This is the first report coming from Arab countries. Additional reports in patients with a progressive course and adult-onset are needed, but this could be the first report of this disease diagnosed in adulthood since it is a disease of children and adolescents. In addition, our patients had epileptic seizures, which were not previously documented in patients with CWF19L1 mutations. We postulate that mutations in this gene have widespread functional and structural changes in multiple levels of the neuraxis rather than being a pure cerebellar disorder.

KEYWORDS:

• CWF19L1
• autosomal recessive cerebellar ataxia 17
• epilepsy
• novel mutation
• Saudi Arabia

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Notes on contributors

Hussein Algahtani

Hussein Algahtani is a consultant neurologist at King Abdulaziz Medical City in Jeddah, Saudi Arabia. He is also an associate professor in neurology in the college of medicine at King Saud bin Abdulaziz University for Health Sciences in Jeddah, Saudi Arabia.

Bader Shirah

Bader Shirah is a graduate of the college of medicine at King Saud bin Abdulaziz University for Health Sciences in Jeddah, Saudi Arabia.

Samah Almatrafi

Samah Almatrafi is a graduate of the college of medicine at King Saud bin Abdulaziz University for Health Sciences in Jeddah, Saudi Arabia.

Mohammad H. Al-Qahtani

Mohammad H. Al-Qahtani is a geneticists from the Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.

Angham Abdulrahman Abdulkareem

Angham Abdulrahman Abdulkareem is a geneticists from the Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.

Muhammad Imran Naseer

Muhammad Imran Naseer is geneticists from the Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.