#605280
Table of Contents
A number sign (#) is used with this entry because of evidence that spastic paraplegia-13 (SPG13) is caused by heterozygous mutation in the HSPD1 (118190) on chromosome 2q33.
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Fontaine et al. (2000) reported a large family of French descent with autosomal dominant pure spastic paraplegia. They excluded genetic linkage to known loci for this general phenotype and performed a genomewide search. They found evidence for linkage of the disorder (SPG13) to polymorphic markers on 2q24-q34, with a maximum lod score of 3.0 with marker D2S2318.
Fontaine et al. (2000) compared the clinical features of the French family showing linkage to 2q24 with those of 12 families showing linkage to 2p (SPG4; 182601). The SPG13 family had significantly more patients without Babinski signs, with increased reflexes in the upper limbs, and with severe functional handicaps. Fontaine et al. (2000) noted that the gene for autosomal recessive symmetric spastic cerebral palsy had been mapped to 2q24-q25. Although this disease differs from SPG13 in clinical presentation and in mode of inheritance, the authors could not exclude the possibility that the disorders represent allelic mutations of the same gene. The 2 mapping regions overlap and both disorders affect the pyramidal tracts.
The transmission pattern of SPG13 in the family reported by Fontaine et al. (2000) and Hansen et al. (2002) was consistent with autosomal dominant inheritance.
Hansen et al. (2002) found a heterozygous mutation in HSPD1 gene (118190.0001) in affected members of the family with SPG13 reported by Fontaine et al. (2000).
Hansen et al. (2007) screened 23 unrelated Danish patients with SPG for mutations in the HSPD1 gene and identified heterozygosity for a missense mutation (Q461E; 118190.0003) in 1 patient. The variant was not present in 400 unrelated Danish control individuals. Age of symptom onset in the patient was 52 years. Her 2 brothers, aged 56 and 65, also carried the mutation, but did not exhibit SPG manifestations. However, their deceased mother had a gait disturbance similar to that in the proband, suggesting reduced penetrance of the mutation.
Fontaine, B., Davoine, C.-S., Durr, A., Paternotte, C., Feki, I., Weissenbach, J., Hazan, J., Brice, A. A new locus for autosomal dominant pure spastic paraplegia, on chromosome 2q24-q34. Am. J. Hum. Genet. 66: 702-707, 2000. [PubMed: 10677329, images, related citations] [Full Text]
Hansen, J. J., Durr, A., Cournu-Rebeix, I., Georgopoulos, C., Ang, D., Nielsen, M. N., Davoine, C.-S., Brice, A., Fontaine, B., Gregersen, N., Bross, P. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am. J. Hum. Genet. 70: 1328-1332, 2002. [PubMed: 11898127, images, related citations] [Full Text]
Hansen, J., Svenstrup, K., Ang, D., Nielsen, M. N., Christensen, J. H., Gregersen, N., Nielsen, J. E., Georgopoulos, C., Bross, P. A novel mutation in the HSPD1 gene in a patient with hereditary spastic paraplegia. J. Neurol. 254: 897-900, 2007. [PubMed: 17420924, related citations] [Full Text]
SNOMEDCT: 783698005; ORPHA: 100994; DO: 0110766;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q33.1 | Spastic paraplegia 13, autosomal dominant | 605280 | Autosomal dominant | 3 | HSPD1 | 118190 |
A number sign (#) is used with this entry because of evidence that spastic paraplegia-13 (SPG13) is caused by heterozygous mutation in the HSPD1 (118190) on chromosome 2q33.
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Fontaine et al. (2000) reported a large family of French descent with autosomal dominant pure spastic paraplegia. They excluded genetic linkage to known loci for this general phenotype and performed a genomewide search. They found evidence for linkage of the disorder (SPG13) to polymorphic markers on 2q24-q34, with a maximum lod score of 3.0 with marker D2S2318.
Fontaine et al. (2000) compared the clinical features of the French family showing linkage to 2q24 with those of 12 families showing linkage to 2p (SPG4; 182601). The SPG13 family had significantly more patients without Babinski signs, with increased reflexes in the upper limbs, and with severe functional handicaps. Fontaine et al. (2000) noted that the gene for autosomal recessive symmetric spastic cerebral palsy had been mapped to 2q24-q25. Although this disease differs from SPG13 in clinical presentation and in mode of inheritance, the authors could not exclude the possibility that the disorders represent allelic mutations of the same gene. The 2 mapping regions overlap and both disorders affect the pyramidal tracts.
The transmission pattern of SPG13 in the family reported by Fontaine et al. (2000) and Hansen et al. (2002) was consistent with autosomal dominant inheritance.
Hansen et al. (2002) found a heterozygous mutation in HSPD1 gene (118190.0001) in affected members of the family with SPG13 reported by Fontaine et al. (2000).
Hansen et al. (2007) screened 23 unrelated Danish patients with SPG for mutations in the HSPD1 gene and identified heterozygosity for a missense mutation (Q461E; 118190.0003) in 1 patient. The variant was not present in 400 unrelated Danish control individuals. Age of symptom onset in the patient was 52 years. Her 2 brothers, aged 56 and 65, also carried the mutation, but did not exhibit SPG manifestations. However, their deceased mother had a gait disturbance similar to that in the proband, suggesting reduced penetrance of the mutation.
Fontaine, B., Davoine, C.-S., Durr, A., Paternotte, C., Feki, I., Weissenbach, J., Hazan, J., Brice, A. A new locus for autosomal dominant pure spastic paraplegia, on chromosome 2q24-q34. Am. J. Hum. Genet. 66: 702-707, 2000. [PubMed: 10677329] [Full Text: https://doi.org/10.1086/302776]
Hansen, J. J., Durr, A., Cournu-Rebeix, I., Georgopoulos, C., Ang, D., Nielsen, M. N., Davoine, C.-S., Brice, A., Fontaine, B., Gregersen, N., Bross, P. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am. J. Hum. Genet. 70: 1328-1332, 2002. [PubMed: 11898127] [Full Text: https://doi.org/10.1086/339935]
Hansen, J., Svenstrup, K., Ang, D., Nielsen, M. N., Christensen, J. H., Gregersen, N., Nielsen, J. E., Georgopoulos, C., Bross, P. A novel mutation in the HSPD1 gene in a patient with hereditary spastic paraplegia. J. Neurol. 254: 897-900, 2007. [PubMed: 17420924] [Full Text: https://doi.org/10.1007/s00415-006-0470-y]
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