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Whole exome sequencing identifies novel variant underlying hereditary spastic paraplegia in consanguineous Pakistani families
- Source :
- Journal of Clinical Neuroscience. 67:19-23
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Hereditary Spastic paraplegias (HSPs) are heterogeneous group of degenerative disorders characterized by progressive weakness and spasticity of the lower limbs, combined with additional neurological features. This study aimed to identify causative gene variants in two nonrelated consanguineous Pakistani families segregating HSP. Whole exome sequencing (WES) was performed on a total of five individuals from two families including four affected and one phenotypically normal individual. The variants were validated by Sanger sequencing and segregation analysis. In family A, a novel homozygous variant c.604G > A (p.Glu202Lys) was identified in the CYP2U1 gene with clinical symptoms of SPG56 in 3 siblings. Whereas, a previously reported variant c.5769delT (p.Ser1923Argfs*28) in the SPG11 gene was identified in family B manifesting clinical features of SPG11 in 3 affected individuals. Our combined findings add to the clinical and genetic variability associated with CYP2U1 and SPG11 variants highlighting the complexity of HSPs. These findings further emphasize the usefulness of WES as a powerful diagnostic tool.
- Subjects :
- Adult
Male
medicine.medical_specialty
Ataxia
Hereditary spastic paraplegia
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Physiology (medical)
Exome Sequencing
Humans
Medicine
Pakistan
Spasticity
Genetic variability
Child
Cytochrome P450 Family 2
Exome sequencing
Sanger sequencing
Genetics
Spastic Paraplegia, Hereditary
business.industry
Proteins
General Medicine
medicine.disease
Pedigree
Phenotype
Neurology
030220 oncology & carcinogenesis
Mutation
symbols
Medical genetics
Female
Surgery
Neurology (clinical)
CYP2U1
medicine.symptom
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 09675868
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Neuroscience
- Accession number :
- edsair.doi.dedup.....36884073ffaf421da955265f56c12500