Spastic paraplegia 33, autosomal dominant

General Information (adopted from Orphanet):

Synonyms, Signs: SPG33
Number of Symptoms 9
OrphanetNr:
OMIM Id: 610244
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
16826525 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: No data available.

Comment:

Protrudin is a membrane protein that regulates polarized vesicular trafficking in neurons. The protrudin gene (ZFYVE27) is mutated in a subset of individuals with hereditary spastic paraplegia (HSP), and protrudin is therefore also referred to as spastic paraplegia 33 (=SPG33) (PMID:24668814). The mutated ZFYVE27 protein shows an aberrant intracellular pattern in its tubular structure. Its interaction with spastin is severely affected. It is postulated that this specific mutation in ZFYVE27 affects neuronal intracellular trafficking in the corticospinal tract, which is consistent with the pathology of HSP (PMID:16826525).

Symptom Information: Sort by abundance 

1
(HPO:0011448) Ankle clonus 16826525 IBIS 31 / 7739
2
(HPO:0007340) Lower limb muscle weakness Frequent [IBIS] 18413476 IBIS 61 / 7739
3
(HPO:0003487) Babinski sign 16826525 IBIS 179 / 7739
4
(HPO:0001347) Hyperreflexia 16826525 IBIS 363 / 7739
5
(HPO:0002061) Lower limb spasticity 16826525 IBIS 56 / 7739
6
(HPO:0001258) Spastic paraplegia Very frequent [IBIS] 16826525 IBIS 97 / 7739
7
(HPO:0002064) Spastic gait 16826525 IBIS 46 / 7739
8
(HPO:0001288) Gait disturbance 16826525 IBIS 318 / 7739
9
(HPO:0001762) Talipes equinovarus 16826525 IBIS 309 / 7739

Associated genes:

ZFYVE27;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Mannan et al. (2006) described a 5-generation German family with hereditary spastic paraplegia (HSP). Clinical features of affected members suggested that theirs was a pure form of HSP. The index patient had had pes equinus for many years ...
Molecular genetics OMIM In the German family with HSP described by them, Mannan et al. (2006) found a missense mutation in the ZFYVE27 gene (G191V; 610243.0001). The ZFYVE27 gene encodes a FYVE-finger domain protein that interacts with spastin (604277), the protein ...