Genetic and Clinical Features of Hereditary Spastic Paraplegia in Childhood: Identification of Eight Novel Variants

14 Pages Posted: 27 Sep 2023

See all articles by Mehmet Akif Kilic

Mehmet Akif Kilic

Istanbul University

Edibe Pembegul Yildiz

Istanbul University

Adnan Deniz

Kocaeli University

Orhan Coskun

Gaziosmanpasa Taksim Teaching Hospital

Fulya Kurekci

Istanbul University

Rıdvan Avci

Istanbul University

Hulya Maras Genc

Istanbul University

Gozde Yesil

Istanbul University

Sinan Akbas

Istanbul University

Ahmet Yesilyurt

Acibadem Healthcare Group

Bulent Kara

Kocaeli University

Abstract

Background: Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative disorders characterized primarily by progressive spasticity and weakness in the lower limbs. Our objective was to determine the clinical and molecular characteristics of patients with genetically confirmed childhood-onset HSPs and to expand the genetic and clinical spectrum for some rare subtypes of HSP.

Methods: We reviewed the charts of subjects with genetically confirmed childhood-onset HSP followed in two pediatric neurology clinics in Turkiye between 2015 and 2023. The age at the onset of the disease was defined as the point at which the delayed motor milestones were observed. Genetic tests were performed through hereditary spastic paraplegia panel or whole-exome sequencing (WES).

Results: There was a total of 18 patients from 17 families. The median age of symptom onset was 18 months (range, 2 to 84 months). Independent walking was not achieved at 17 months for 67% of patients (n = 12). A total of eight novel variants were described. Two subjects had a novel variant in the GBA2 gene (SPG46), and one subject each had a novel variant in ALS2 (IAHSP), ERLIN1 (SPG62), WASHC5 (SPG8), SPG11 (SPG11), KIF1A (SPG30), GJC2 (SPG44) and HACE1 (SPPRS).

Conclusion: We identified eight novel variants, most of which were found through WES. As a result of the clinical heterogeneity of HSPs, WES may reduce the number of unnecessary diagnostic screening tools used for diagnosis. This study contributes to the expansion of the genetic and clinical spectrum of some rare subtypes of HSP.

Note:
Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Interests: None.

Ethics Approval Statement: The study was approved by the Human Research and Ethics Committees of the Istanbul Medical Faculty (E-29624016-050.99-1983187).

Keywords: Hereditary spastic paraplegia, Developmental delay, genotype-phenotype associations, Whole-exome sequencing, SPG46, SPG11, SPG8, SPG62

Suggested Citation

Kilic, Mehmet Akif and Yildiz, Edibe Pembegul and Deniz, Adnan and Coskun, Orhan and Kurekci, Fulya and Avci, Rıdvan and Genc, Hulya Maras and Yesil, Gozde and Akbas, Sinan and Yesilyurt, Ahmet and Kara, Bulent, Genetic and Clinical Features of Hereditary Spastic Paraplegia in Childhood: Identification of Eight Novel Variants. Available at SSRN: https://ssrn.com/abstract=4581444 or http://dx.doi.org/10.2139/ssrn.4581444

Mehmet Akif Kilic (Contact Author)

Istanbul University ( email )

Edibe Pembegul Yildiz

Istanbul University ( email )

Adnan Deniz

Kocaeli University ( email )

Umuttepe Kampus
Hukuk Fakultesi
Kocaeli, +90
Turkey

Orhan Coskun

Gaziosmanpasa Taksim Teaching Hospital ( email )

Fulya Kurekci

Istanbul University ( email )

Rıdvan Avci

Istanbul University ( email )

Hulya Maras Genc

Istanbul University ( email )

Gozde Yesil

Istanbul University ( email )

Sinan Akbas

Istanbul University ( email )

Ahmet Yesilyurt

Acibadem Healthcare Group ( email )

Bulent Kara

Kocaeli University ( email )

Umuttepe Kampus
Hukuk Fakultesi
Kocaeli, +90
Turkey

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
42
Abstract Views
155
PlumX Metrics