Dataset Information

"Ear of the Lynx" Sign in Hereditary Spastic Paraparesis (HSP) 76.

ABSTRACT:

Background

Hereditary Spastic Paraparesis (HSP) are a group of genetically inherited disorders, clinically and genetically heterogenous and characterized by degeneration of corticospinal tracts, manifesting with progressive spasticity and lower limbs weakness. Most HSPs have an autosomal dominant inheritance. "Ear of the Lynx" sign describes the characteristic abnormality in the forceps minor region of the corpus callosum (CC) on MRI brain. These bear a striking resemblance to the ears of a lynx. This finding has previously been described with hereditary spastic paraparesis 11 and 15, both of which are autosomal recessive HSPs.

Cases

We describe this finding in two siblings with novel mutations causing HSP76, an extremely rare autosomal recessive HSP (less than 50 cases described worldwide), which has not been reported previously.

Conclusion

This sign suggests the presence of pathogenic genetic mutations and is likely indicative of autosomal recessive HSPs.

SUBMITTER: Agarwal A

PROVIDER: S-EPMC9847285 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

"Ear of the Lynx" Sign in Hereditary Spastic Paraparesis (HSP) 76.

Agarwal Ayush A Oinam Rahul R Goel Vinay V Sharma Pooja P Faruq Mohd M Garg Ajay A Srivastava Achal K AK

Movement disorders clinical practice 20221117 1

<h4>Background</h4>Hereditary Spastic Paraparesis <b>(</b>HSP) are a group of genetically inherited disorders, clinically and genetically heterogenous and characterized by degeneration of corticospinal tracts, manifesting with progressive spasticity and lower limbs weakness. Most HSPs have an autosomal dominant inheritance. "Ear of the Lynx" sign describes the characteristic abnormality in the forceps minor region of the corpus callosum (CC) on MRI brain. These bear a striking resemblance to the ...[more]

PMID: 36704071

Similar Datasets

Project description:Hereditary spastic paraparesis type 15 is a recessive complicated form of the disease clinically characterized by slowly progressive spastic paraparesis and mental deterioration with onset between the first and second decade of life. Thinning of corpus callosum is the neuroradiological distinctive sign frequently associated with white matter abnormalities. The causative gene, ZFYVE26, encodes a large protein of 2539 amino acid residues, termed spastizin, containing three recognizable domains: a zinc finger, a leucine zipper and a FYVE domain. Spastizin protein has a diffuse cytoplasmic distribution and co-localizes partially with early endosomes, the endoplasmic reticulum, microtubules and vesicles involved in protein trafficking. In addition, spastizin localizes to the mid-body during the final step of mitosis and contributes to successful cytokinesis. Spastizin interacts with Beclin 1, a protein required for cytokinesis and autophagy, which is the major lysosome-mediated degradation process in the cell. In view of the Beclin 1-spastizin interaction, we investigated the possible role of spastizin in autophagy. We carried out this analysis by using lymphoblast and fibroblast cells derived from four different spastizin mutated patients (p.I508N, p.L243P, p.R1209fsX, p.S1312X) and from control subjects. Of note, the truncating p.R1209fsX and p.S1312X mutations lead to loss of spastizin protein. The results obtained indicate that spastizin interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex and is required for autophagosome maturation. In cells lacking spastizin or with mutated forms of the protein, spastizin interaction with Beclin 1 is lost although the formation of the Beclin 1-UVRAG-Rubicon complex can still be observed. However, in these cells we demonstrate an impairment of autophagosome maturation and an accumulation of immature autophagosomes. Autophagy defects with autophagosome accumulation can be observed also in neuronal cells upon spastizin silencing. These results indicate that autophagy is a central process in the pathogenesis of complicated forms of hereditary spastic paraparesis with thin corpus callosum.

Dataset Information

"Ear of the Lynx" Sign in Hereditary Spastic Paraparesis (HSP) 76.

Background

Cases

Conclusion

Publications

"Ear of the Lynx" Sign in Hereditary Spastic Paraparesis (HSP) 76.

Similar Datasets

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