Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Description of Clinical Features and Genetic Analysis of One Ultra-Rare (Spg64) and Two Common Forms (Spg5a and Spg15) of Hereditary Spastic Paraplegia Families Publisher Pubmed



Pashaei M1 ; Davarzani A1 ; Hajati R1 ; Zamani B2 ; Nafissi S3 ; Larti F1 ; Nilipour Y4 ; Rohani M5 ; Alavi A1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
  2. 2. Neurology Department, Firoozgar hospital, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Neurology, Shariati Hospital., Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Pediatric Pathology Research Center, Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran

Source: Journal of Neurogenetics Published:2021


Abstract

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder, characterized by lower-limb spasticity and weakness. To date, more than 82 loci/genes (SPG1-SPG82) have been identified that contribute to the cause of HSP. Despite the use of next-generation sequencing-based methods, genetic-analysis has failed in the finding of causative genes in more than 50% of HSP patients, indicating a more significant heterogeneity and absence of a given phenotype-genotype correlation. Here, we performed whole-exome sequencing (WES) to identify HSP-causing genes in three unrelated-Iranian probands. Candidate variants were detected and confirmed in the probands and co-segregated in the family members. The phenotypic data gathered and compared with earlier cases with the same sub-types of disease. Three novel homozygous variants, c.978delT; p.Q327Kfs*39, c.A1208G; p.D403G and c.3811delT; p.S1271Lfs*44, in known HSP-causing genes including ENTPD1, CYP7B1, and ZFYVE26 were identified, respectively. Intra and interfamilial clinical variability were observed among affected individuals. Mutations in CYP7B1 and ZFYVE26 are relatively common causes of HSP and associated with SPG5A and SPG15, respectively. However, mutations in ENTPD1 are related to SPG64 which is an ultra-rare form of HSP. The research affirmed more complexities of phenotypic manifestations and allelic heterogeneity in HSP. Due to these complexities, it is not feasible to show a clear phenotype-genotype correlation in HSP cases. Identification of more families with mutations in HSP-causing genes may help the establishment of this correlation, further understanding of the molecular basis of the disease, and would provide an opportunity for genetic-counseling in these families. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
Related Docs
View other Related Docs
1. Description of Combined Arhsp/Jals Phenotype in Some Patients With Spg11 Mutations, Molecular Genetics and Genomic Medicine (2020)
2. A Case Report of Concurrent Occurrence of Two Inherited Axonopathies Within a Family: The Benefit of Whole-Exome Sequencing, International Journal of Neuroscience (2023)
3. Molecular Diagnosis of Hereditary Neuropathies by Whole Exome Sequencing and Expanding the Phenotype Spectrum, Archives of Iranian Medicine (2020)
4. Three Iranian Patients With Rare Subtypes of Hereditary Spastic Paraplegia (Hsp): Spg76, Spg56, and Spg69, Neurogenetics (2025)
5. Bi-Allelic Variants in Rnf170 Are Associated With Hereditary Spastic Paraplegia, Nature Communications (2019)
6. Genotype-Phenotype Correlation and Description of Two Novel Mutations in Iranian Patients With Glycogen Storage Disease 1B (Gsd1b), Orphanet Journal of Rare Diseases (2020)
7. Clinical Application of Next Generation Sequencing for Mendelian Disease Diagnosis in the Iranian Population, npj Genomic Medicine (2024)
8. Copy Number Variations in Hereditary Spastic Paraplegia-Related Genes: Evaluation of an Iranian Hereditary Spastic Paraplegia Cohort and Literature Review, Molecular Syndromology (2023)
Experts (# of related papers)
View all Related Experts
Farzad Fatehi (2)
Shahriar Nafissi (2)
Other Related Docs
9. Identification of a Novel Truncating Variant in Ahi1 Gene and a Brief Review on Mutations Spectrum, Molecular Biology Reports (2021)
10. Identification of Eleven Different Mutations Including Six Novel, in the Arylsulfatase B Gene in Iranian Patients With Mucopolysaccharidosis Type Vi, Molecular Biology Reports (2019)
11. Whole Genome Sequencing Identifies a Novel Homozygous Exon Deletion in the Nt5c2 Gene in a Family With Intellectual Disability and Spastic Paraplegia, npj Genomic Medicine (2017)
12. Genetic Homogeneity of a Tdp1 Variant, C.1478A>G, As the Main Disease-Causing Variant of Spinocerebellar Ataxia With Axonal Neuropathy 1 (Scan1) in the Middle East: A Systematic Review, Pediatric Neurology (2025)
13. Clinical Spectrum in Multiple Families With Primary Coq10 Deficiency, American Journal of Medical Genetics# Part A (2021)
14. Clinical and Molecular Assessment of a Spastic Ataxia 4 (Spax4) Patient With a Novel Variant in the Mtpap Gene, and a Systematic Review, Gene (2025)