Affiliation:
1. Diagnostics Division Centre for DNA Fingerprinting and Diagnostics Hyderabad Telangana India
2. Graduate Studies Regional Centre for Biotechnology Faridabad Haryana India
3. Department of Medical Genetics Nizam's Institute of Medical Sciences Hyderabad Telangana India
Abstract
AbstractBackgroundHereditary spastic paraplegia 81 is a recently identified, rare autosomal recessive disease, caused by biallelic pathogenic variants in the SELENOI gene, with only two families reported to date. The features documented in the two previous affected families include sensorineural deafness, blindness, cleft palate, delayed motor development, regression of motor skills, impaired intellectual development, poor speech and language acquisition, spasticity, hyperreflexia, white matter abnormalities and cerebral and cerebellar atrophy.MethodsIn the present study, we performed exome sequencing analysis in a single family with two affected siblings to identify the genetic cause of complicated hereditary spastic paraplegia. The results were further confirmed by Sanger sequencing, cDNA analysis and 3D protein modelling.ResultsExome sequencing identified a homozygous, synonymous variant in the SELENOI gene (NM_033505.4:c.126G>A:p.(Lys42Lys)) in both of the siblings. Sanger sequencing confirmed the heterozygous status in both parents consistent with the autosomal recessive inheritance. This variant has been found to disrupt normal splicing and lead to skipping of exon 2, causing in‐frame deletion of SELENOI N‐terminal 23 amino acids [NM_033505.4:c.57_126del:p.(Tyr20_Lys42del)] and further leading to structural changes in the protein.ConclusionsWe report a novel homozygous synonymous variant in the SELENOI gene causing abnormal splicing in two patients affected with hereditary spastic paraplegia 81. This report further expands the phenotypic and genotypic spectrum of hereditary spastic paraplegia 81.
Funder
Department of Biotechnology, Ministry of Science and Technology, India
Subject
Genetics (clinical),Drug Discovery,Genetics,Molecular Biology,Molecular Medicine
Cited by
1 articles.
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