# Children with Genetically Confirmed Hereditary Spastic Paraplegia: A Single-Center Experience

## TL;DR

This study reports new genetic mutations and clinical features in children with hereditary spastic paraplegia, improving diagnosis and understanding of the condition.

## Contribution

The study identifies novel mutations and expands the known inheritance patterns and clinical phenotypes of hereditary spastic paraplegia.

## Key findings

- Heterozygous mutations in GBA2 and SPG11 are reported for the first time, expanding inheritance patterns.
- A novel homozygous C19orf12 mutation causes brain iron accumulation, broadening genetic and clinical understanding.
- New TFG gene mutations and a CYP7B1 variant are identified, contributing to the genetic diversity of HSP.

## Abstract

What are the main findings?
We identified a new inheritance pattern, a novel variants and a different clinical phenotype in some forms of hereditary spastic paraplegia.

We identified a new inheritance pattern, a novel variants and a different clinical phenotype in some forms of hereditary spastic paraplegia.

What is the implication of the main finding?
The new inheritance patterns, new variants and phenotypes identified will contribute to the clinical and genetic diagnosis and monitoring of HSP.

The new inheritance patterns, new variants and phenotypes identified will contribute to the clinical and genetic diagnosis and monitoring of HSP.

Objective: The classification of hereditary spastic paraplegia (HSP) is based on genetics, and the number of genetic loci continues to increase with new genetic descriptions. Additionally, the number of new variants in known mutations continues to increase. In this paper, we aim to report our experience with genetically confirmed HSPs. Methods: We retrospectively evaluated 10 consecutive children with genetically confirmed HSPs. Results: In this study, we identified six novel mutations, including spastic paraplegia 11 (SPG11), glucosylceramidase beta 2 (GBA2), chromosome 19 open reading frame 12 (C19orf12), 1 in each of the Cytochrome P450 family 7 subfamily B member 1 (CYP7B1) genes, and two different mutations in the intropomyosin-receptor kinase fused gene (TFG) gene. We also identified different clinical phenotypes associated with known mutations. Conclusions: Heterozygous mutations with GBA2 and SPG11 mutation-related HSP are reported for the first time, expanding the known inheritance patterns. We report a novel homozygous chromosome 19 open reading frame 12 (C19orf12) mutation resulting in iron accumulation in the brain, broadening the genetic variants and clinical findings. We determine the first Turkish patients with carnitine palmitoyltransferase IC (CPT1C) and TFG gene mutation-related pure HSP. A pure form of HSP with two novel TFG gene mutations is also identified for the first time. We report the first Turkish patient with kinase D-interacting substrate of 220 kDa (KIDINS220) gene, broadening the clinical spectrum of KIDINS220 variant-related disorders to encompass certain HSPs. Moreover, a novel variant in the oxysterol7-hydroxylase (CYP7B1) gene is reported, expanding the genetic variants and clinical findings relating to SPG5.