Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing
Yoshinori Tsurusaki1, Hitoshi Osaka, Haruka Hamanoue
1Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Journal of Medical Genetics
|March 19, 2011
Summary
Exome sequencing identified a novel MCT8 mutation in a family with X-linked leucoencephalopathy. This genetic finding aids in diagnosing rare neurological disorders and highlights advanced sequencing for genetic mutation discovery.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- X-linked leucoencephalopathy is a rare neurological disorder with unknown etiology in this family.
- Conventional PCR sequencing of candidate genes did not identify the causative mutation.
Purpose of the Study:
- To investigate the genetic cause of X-linked leucoencephalopathy in a family using exome sequencing.
- To analyze all transcripts of the X chromosome for potential mutations.
Main Methods:
- Whole X chromosome exome sequencing was performed on affected and unaffected male subjects.
- Liquid-based genome partitioning was used prior to next-generation sequencing.
- Subsequent PCR-based sequencing confirmed mutations in family members.
Main Results:
- A nonsense mutation (c.1102A→T (p.R368X)) in the MCT8 gene was identified in the proband.
- The mutation was confirmed in other affected males (hemizygous) and carrier females (heterozygous).
- The proband exhibited neurological symptoms without abnormal thyroid function, atypical for MCT8 mutations.
Conclusions:
- Single-lane exome sequencing effectively analyzes X chromosome transcripts for mutation screening.
- This approach is highly suitable for identifying mutations in X-linked recessive disorders.
- Exome sequencing avoids candidate gene selection bias, improving diagnostic yield.
