Ann Rehabil Med.  2016 Dec;40(6):1129-1134. 10.5535/arm.2016.40.6.1129.

Identification of a Heterozygous SPG11 Mutation by Clinical Exome Sequencing in a Patient With Hereditary Spastic Paraplegia: A Case Report

• Oh JY
• Do HJ
• Lee S
• Jang JH
• Cho EH
• Jang DH

• KMID: 2371347
• DOI: http://doi.org/10.5535/arm.2016.40.6.1129

Abstract

Next-generation sequencing, such as whole-genome sequencing, whole-exome sequencing, and targeted panel sequencing have been applied for diagnosis of many genetic diseases, and are in the process of replacing the traditional methods of genetic analysis. Clinical exome sequencing (CES), which provides not only sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to genetic diagnosis. Sequencing of genes with clinical relevance rather than whole exome sequencing might be more suitable for the diagnosis of known hereditary disease with genetic heterogeneity. Here, we present the clinical usefulness of CES for the diagnosis of hereditary spastic paraplegia (HSP). We report a case of patient who was strongly suspected of having HSP based on her clinical manifestations. HSP is one of the diseases with high genetic heterogeneity, the 72 different loci and 59 discovered genes identified so far. Therefore, traditional approach for diagnosis of HSP with genetic analysis is very challenging and time-consuming. CES with TruSight One Sequencing Panel, which enriches about 4,800 genes with clinical relevance, revealed compound heterozygous mutations in SPG11. One workflow and one procedure can provide the results of genetic analysis, and CES with enrichment of clinically relevant genes is a cost-effective and time-saving diagnostic tool for diseases with genetic heterogeneity, including HSP.

Keyword

Hereditary spastic paraplegia; Exome; Genes

MeSH Terms

Diagnosis
Exome*
Genetic Diseases, Inborn
Genetic Heterogeneity
Humans
Spastic Paraplegia, Hereditary*

Figure

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  Fig. 1 Pedigree of the family of the 17-year-old female with spastic paraplegia. The black symbol represents the patient. The index I-3 died due to old age, and the index II-6 passed away at an early age due to an unknown cause.

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  Fig. 2 Brain magnetic resonance imaging findings in the patient. (A) Sagittal T1-weighted image reveals a thin corpus callosum. (B) Axial T2-weighted image also shows a thin corpus callosum.

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  Fig. 3 DNA sequence chromatography for the patient and her family. (A) Heterozygous c.3036C>A mutations in the patient, her father and sister. (B) Heterozygous c.3291+1G>T mutations in the patient and her mother.

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