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

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Hereditary spastic paraplegia (HSP) classification relies on genetics, with an increasing number of identified genetic loci and variants.
• Accurate genetic diagnosis is crucial for understanding HSP's diverse clinical spectrum.

Purpose of the Study:

• To report the clinical and genetic findings of 10 children with genetically confirmed HSP.
• To identify novel mutations and expand the genotypic and phenotypic spectrum of HSP.

Main Methods:

• Retrospective evaluation of 10 pediatric patients with genetically confirmed HSP.
• Genetic analysis to identify mutations in known and novel HSP-related genes.

Main Results:

• Six novel mutations were identified in SPG11, GBA2, C19orf12, CYP7B1, and TFG genes.
• New inheritance patterns for GBA2 and SPG11 mutations were observed.
• A novel homozygous C19orf12 mutation linked to brain iron accumulation was found.
• First Turkish patients with CPT1C and TFG gene mutations causing pure HSP were identified.
• Novel TFG gene mutations associated with pure HSP and a novel CYP7B1 variant were reported.

Conclusions:

• The genetic landscape of HSP is expanding with the discovery of novel mutations and inheritance patterns.
• Genetic confirmation aids in broadening the clinical spectrum and understanding of HSP-related disorders.
• This study contributes significant findings to the genetic basis of HSP, particularly in the Turkish population.