Hereditary spastic paraplegia (SPG 48) with deafness and azoospermia: A case report

Area of Science:

• Neurogenetics
• Molecular Biology
• Neurology

Background:

• Hereditary spastic paraplegias (HSP) are a group of inherited neurodegenerative disorders.
• SPG48 is a rare genotype linked to mutations in the AP5Z1 gene, crucial for intracellular membrane trafficking.

Observation:

• A 53-year-old male patient presented with spastic paraplegia, infertility, cognitive deficits, and peripheral neuropathy.
• Brain MRI revealed mild atrophy and white matter lesions.
• Auditory threshold analysis showed significant bilateral hearing impairment.

Findings:

• Sanger sequencing identified a homozygous deletion in the chr 7:4785904-4786677 region of the AP5Z1 gene.
• This deletion resulted in a premature stop codon in exon 10.
• The patient's brother was found to be heterozygous for the identified mutation.

Implications:

• This case expands the clinical and genetic spectrum of SPG48.
• Highlights the role of AP5Z1 mutations in complex neurological and sensory phenotypes.
• Contributes to understanding the pathophysiology of inherited neurodegenerative disorders.