Identify mutation in amyotrophic lateral sclerosis cases using HaloPlex target enrichment system
Zhi-Jun Liu1, Hong-Fu Li2, Guo-He Tan3
1Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
Neurobiology of Aging
|August 12, 2014
Summary
This study used HaloPlex targeted sequencing to screen 18 amyotrophic lateral sclerosis (ALS) genes in 8 patients. The approach identified known SOD1 mutations and a novel DCTN1 mutation, aiding molecular diagnosis.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Amyotrophic lateral sclerosis (ALS) presents significant diagnostic challenges due to clinical and genetic heterogeneity.
- Over 18 causative genes are known, complicating molecular diagnosis.
- Targeted sequencing offers a method to screen known and candidate genes efficiently.
Observation:
- The HaloPlex target enrichment system was employed to screen 18 ALS-associated genes in 8 ALS patient samples.
- An average of 9.5 synonymous or missense mutations were detected per sample.
- Sanger sequencing validated the findings.
Findings:
- Three documented SOD1 mutations (p.F21C, p.G148D, p.C147R) were identified in ALS probands.
- A novel DCTN1 mutation (p.G59R) was discovered in one proband and segregated with the disease.
- The mutation was absent in 200 control subjects.
Implications:
- The HaloPlex system demonstrates high throughput and efficiency for ALS genetic screening.
- This targeted sequencing approach shows promise for clinical molecular diagnosis of ALS.
- The methodology is applicable to other inherited diseases with multiple genetic contributors.
