HSN w/SPG

CCT5 | 2006

What Is HSN w/SPG?

HSN w/SPG is a type of CMT caused by autosomal recessive mutations in the CCT5 gene. This gene provides instructions for making a component of a protein-folding complex that helps other proteins achieve their correct shape within nerve cells. Mutations in the CCT5 gene disrupt this function, leading to impaired nerve signal transmission.

HSN w/SPG is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.

Clinical Features

Symptoms of HSN w/SPG combine a sensory neuropathy with spastic paraplegia, meaning that sensory loss occurs alongside stiffness and weakness of the legs from involvement of the upper motor neurons. Nerve conduction studies reflect a sensory and axonal process.

HSN w/SPG symptoms may include:

  • Reduced sensation in the feet and lower legs
  • Leg stiffness and spasticity
  • Progressive weakness of the lower limbs
  • A spastic gait
  • Painless injuries from reduced sensation
  • Foot drop
  • Additional symptoms not listed here

Disease Course

HSN w/SPG shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.

Clinical Basics

Subtype
HSN w/SPG

Classification
HSN

Neuropathy Type
Axonal

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
CCT5

Gene Full Name
chaperonin containing TCP1 subunit 5

HGNC Gene Alias(es)
CCTE, KIAA0098

Chromosome
5p15.2

Zygosity of Responsible Variant
Homozygous

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Hypomorphic

Confidence:
Medium

Prediction:
One recurrent chaperonin substitution carries this subtype, and the literature predicts recessive loss of function: the homozygous CCT5 His147Arg change alters a subunit of the CCT/TRiC folding chamber, reducing the complex's capacity to fold actin, tubulin, and other obligate clients in long sensory and corticospinal axons. Two defective copies are required for the mutilating sensory loss with spastic paraplegia, and restoring folding-competent CCT5 is predicted to rescue.

Rationale:
A subunit of a hetero-oligomeric ring is the classic setting for interference, so a dominant-negative effect is worth entertaining here, but heterozygous relatives are unaffected and the phenotype requires homozygosity. How much folding activity a His147Arg-containing ring retains has not been fully resolved, and that gap sets the grade at medium.

ClinVar Pathogenic Variants

View CCT5 ClinVar Variants

HSN w/SPG OMIM Entry

HSN w/SPG OMIM

CCT5 OMIM Entry

CCT5 OMIM

More Info

HSN w/SPG Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Autosomal recessive mutilating sensory neuropathy with spastic paraplegia maps to chromosome 5p15.31-14.1

Authors

Bouhouche, A., Benomar, A., Bouslam, N., Ouazzani, R., Chkili, T., & Yahyaoui, M.

Publication Date
February 1, 2006

Updated: July 18, 2026 | By: K. Raymond

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