#620607
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-30B (SPG30B) is caused by homozygous mutation in the KIF1A gene (601255) on chromosome 2q37.
Biallelic mutation in the KIF1A gene can also cause hereditary sensory neuropathy type IIC (HSN2C; 614213).
Heterozygous mutation in the KIF1A gene can cause autosomal dominant spastic paraplegia-30A (SPG30A; 610357).
Autosomal recessive spastic paraplegia-30B (SPG30B) is a neurologic disorder characterized by onset of slowly progressive spastic paraplegia with variable age of onset, but usually in the first or second decades of life. Affected individuals have unsteady spastic gait and hyperreflexia of the lower limbs. Most patients have a 'pure' form of the disorder, limited to spastic paraplegia, whereas others may have a 'complicated' form that includes peripheral sensorimotor neuropathy, distal muscle atrophy of the lower limbs, saccadic ocular pursuit, urinary sphincter problems, and/or mild cerebellar signs and symptoms. The phenotypic features represent a spectrum of abnormalities of the central, peripheral, and autonomic nervous system (Klebe et al., 2006; Erlich et al., 2011).
For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Klebe et al. (2006) reported a consanguineous family of Algerian origin in which 4 sibs had hereditary spastic paraplegia. Mean age at onset of stiff legs and unsteady spastic gait was 17.5 years (range 12 to 21). Other clinical features included hyperreflexia of the lower limbs and extensor plantar responses. Two sibs had distal sensory loss, primarily pinprick sensation, and 2 had saccadic ocular movements. Three sibs had subtle cerebellar signs, including ataxia, and subsequent brain imaging of 1 of them showed mild diffuse cerebellar atrophy. Disease progression was slow; all patients remained ambulatory for up to 15 years after disease onset. Klebe et al. (2006) concluded that the disorder in this family was a form of complicated SPG with cerebellar involvement and peripheral neuropathy. Klebe et al. (2012) provided follow-up of the spastic paraplegia family reported by Klebe et al. (2006). The disorder showed slow progression and all patients were still able to walk after disease duration of 9 to 22 years, although maximal walking distance was reduced.
Erlich et al. (2011) reported 3 Palestinian sibs with early childhood onset of slowly progressive spastic paraplegia. They were examined at ages 20, 15, and 14 years, respectively. Although they could participate in sports in childhood, symptoms became more severe between ages 10 and 13 years, and the patients could no longer play, run, or walk long distances. Physical examination showed scissoring gait, lower limb spasticity, hyperreflexia, and extensor plantar responses, most severe in the oldest patient. None had weakness, distal sensory loss, or cognitive dysfunction.
Klebe et al. (2012) reported a consanguineous Palestinian family with genetically confirmed SPG30. Age at onset was available for only 3 patients, and occurred at ages 10, 11, and 39 years. All patients had spasticity with hyperreflexia and extensor plantar responses. Most had distal muscle wasting and weakness as well as impaired pinprick and vibration sense. Two patients tested had an axonal sensorimotor peripheral neuropathy, and brain imaging of these 2 patients was normal. None had saccadic ocular pursuit or sphincter disturbances.
The transmission pattern of SPG30B in the families reported by Klebe et al. (2006) and Erlich et al. (2011) was consistent with autosomal recessive inheritance.
In an Algerian family with autosomal recessive spastic paraplegia, Klebe et al. (2006) found linkage to a 5.1-cM interval, termed SPG30, on chromosome 2q37.3 (maximum multipoint lod score of 3.8 between markers D2S2338 and D2S2585). Direct sequencing excluded mutations in the coding regions of the STK25 gene (602255).
By homozygosity mapping, exome sequencing, and examination of candidate genes, Erlich et al. (2011) identified a homozygous mutation in the KIF1A gene (A255V; 601255.0001) in 3 Palestinian sibs with autosomal recessive spastic paraplegia.
Klebe et al. (2012) identified a homozygous mutation in the KIF1A gene (R350G; 601255.0005) in affected members of a consanguineous Algerian family with SPG30B originally reported by Klebe et al. (2006). Another Palestinian family with the disorder was found to be homozygous for the A255V mutation.
Erlich, Y., Edvardson, S., Hodges, E., Zenvirt, S., Thekkat, P., Shaag, A., Dor, T., Hannon, G. J., Elpeleg, O. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res. 21: 658-664, 2011. [PubMed: 21487076, images, related citations] [Full Text]
Klebe, S., Azzedine, H., Durr, A., Bastien, P., Bouslam, N., Elleuch, N., Forlani, S., Charon, C., Koenig, M., Melki, J., Brice, A., Stevanin, G. Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3. Brain 129: 1456-1462, 2006. [PubMed: 16434418, related citations] [Full Text]
Klebe, S., Lossos, A., Azzedine, H., Mundwiller, E., Sheffer, R., Gaussen, M., Marelli, C., Nawara, M., Carpentier, W., Meyer, V., Rastetter, A., Martin, E., and 11 others. KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations. Europ. J. Hum. Genet. 20: 645-649, 2012. [PubMed: 22258533, related citations] [Full Text]
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q37.3 | Spastic paraplegia 30, autosomal recessive | 620607 | Autosomal recessive | 3 | KIF1A | 601255 |
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-30B (SPG30B) is caused by homozygous mutation in the KIF1A gene (601255) on chromosome 2q37.
Biallelic mutation in the KIF1A gene can also cause hereditary sensory neuropathy type IIC (HSN2C; 614213).
Heterozygous mutation in the KIF1A gene can cause autosomal dominant spastic paraplegia-30A (SPG30A; 610357).
Autosomal recessive spastic paraplegia-30B (SPG30B) is a neurologic disorder characterized by onset of slowly progressive spastic paraplegia with variable age of onset, but usually in the first or second decades of life. Affected individuals have unsteady spastic gait and hyperreflexia of the lower limbs. Most patients have a 'pure' form of the disorder, limited to spastic paraplegia, whereas others may have a 'complicated' form that includes peripheral sensorimotor neuropathy, distal muscle atrophy of the lower limbs, saccadic ocular pursuit, urinary sphincter problems, and/or mild cerebellar signs and symptoms. The phenotypic features represent a spectrum of abnormalities of the central, peripheral, and autonomic nervous system (Klebe et al., 2006; Erlich et al., 2011).
For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Klebe et al. (2006) reported a consanguineous family of Algerian origin in which 4 sibs had hereditary spastic paraplegia. Mean age at onset of stiff legs and unsteady spastic gait was 17.5 years (range 12 to 21). Other clinical features included hyperreflexia of the lower limbs and extensor plantar responses. Two sibs had distal sensory loss, primarily pinprick sensation, and 2 had saccadic ocular movements. Three sibs had subtle cerebellar signs, including ataxia, and subsequent brain imaging of 1 of them showed mild diffuse cerebellar atrophy. Disease progression was slow; all patients remained ambulatory for up to 15 years after disease onset. Klebe et al. (2006) concluded that the disorder in this family was a form of complicated SPG with cerebellar involvement and peripheral neuropathy. Klebe et al. (2012) provided follow-up of the spastic paraplegia family reported by Klebe et al. (2006). The disorder showed slow progression and all patients were still able to walk after disease duration of 9 to 22 years, although maximal walking distance was reduced.
Erlich et al. (2011) reported 3 Palestinian sibs with early childhood onset of slowly progressive spastic paraplegia. They were examined at ages 20, 15, and 14 years, respectively. Although they could participate in sports in childhood, symptoms became more severe between ages 10 and 13 years, and the patients could no longer play, run, or walk long distances. Physical examination showed scissoring gait, lower limb spasticity, hyperreflexia, and extensor plantar responses, most severe in the oldest patient. None had weakness, distal sensory loss, or cognitive dysfunction.
Klebe et al. (2012) reported a consanguineous Palestinian family with genetically confirmed SPG30. Age at onset was available for only 3 patients, and occurred at ages 10, 11, and 39 years. All patients had spasticity with hyperreflexia and extensor plantar responses. Most had distal muscle wasting and weakness as well as impaired pinprick and vibration sense. Two patients tested had an axonal sensorimotor peripheral neuropathy, and brain imaging of these 2 patients was normal. None had saccadic ocular pursuit or sphincter disturbances.
The transmission pattern of SPG30B in the families reported by Klebe et al. (2006) and Erlich et al. (2011) was consistent with autosomal recessive inheritance.
In an Algerian family with autosomal recessive spastic paraplegia, Klebe et al. (2006) found linkage to a 5.1-cM interval, termed SPG30, on chromosome 2q37.3 (maximum multipoint lod score of 3.8 between markers D2S2338 and D2S2585). Direct sequencing excluded mutations in the coding regions of the STK25 gene (602255).
By homozygosity mapping, exome sequencing, and examination of candidate genes, Erlich et al. (2011) identified a homozygous mutation in the KIF1A gene (A255V; 601255.0001) in 3 Palestinian sibs with autosomal recessive spastic paraplegia.
Klebe et al. (2012) identified a homozygous mutation in the KIF1A gene (R350G; 601255.0005) in affected members of a consanguineous Algerian family with SPG30B originally reported by Klebe et al. (2006). Another Palestinian family with the disorder was found to be homozygous for the A255V mutation.
Erlich, Y., Edvardson, S., Hodges, E., Zenvirt, S., Thekkat, P., Shaag, A., Dor, T., Hannon, G. J., Elpeleg, O. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res. 21: 658-664, 2011. [PubMed: 21487076] [Full Text: https://doi.org/10.1101/gr.117143.110]
Klebe, S., Azzedine, H., Durr, A., Bastien, P., Bouslam, N., Elleuch, N., Forlani, S., Charon, C., Koenig, M., Melki, J., Brice, A., Stevanin, G. Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3. Brain 129: 1456-1462, 2006. [PubMed: 16434418] [Full Text: https://doi.org/10.1093/brain/awl012]
Klebe, S., Lossos, A., Azzedine, H., Mundwiller, E., Sheffer, R., Gaussen, M., Marelli, C., Nawara, M., Carpentier, W., Meyer, V., Rastetter, A., Martin, E., and 11 others. KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations. Europ. J. Hum. Genet. 20: 645-649, 2012. [PubMed: 22258533] [Full Text: https://doi.org/10.1038/ejhg.2011.261]
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