Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation analysis

Falco, Michele; Scuderi, Carmela; Musumeci, S; Sturnio, Maurizio; Neri, Marcella; Bigoni, Stefania; Caniatti, Luisa; Fichera, Marco

doi:10.1016/j.nmd.2004.05.017

Cited by 19 publications

(5 citation statements)

References 10 publications

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“…We identified 30 mutations in SPAST in 33 HSP patients (Table 2). Of the 30 mutations, 18 were novel while 12 have been previously described (14–19). Two patients (families 25028 and 2345) each harbored two separate mutations in SPAST ; however, we had no DNA available to test whether these changes occur on the same of opposite chromosomes.…”

Section: Resultsmentioning

confidence: 99%

Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia

et al. 2010

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Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. Over 40 chromosomal loci have been identified for autosomal dominant, recessive, and X-linked HSP. Mutations in the genes atlastin, spastin and REEP1 are estimated to account for up to 50% of autosomal dominant HSP and currently guide the molecular diagnosis of HSP. Here we report the mutation screening results of 120 HSP patients from North America for spastin, atlastin, and REEP1, with the latter one partially reported previously. We identified mutations in 36.7% of all tested HSP patients and describe 20 novel changes in spastin and atlastin. Our results add to a growing number of HSP disease associated variants and confirm the high prevalence of atlastin, spastin, and REEP1 mutations in the HSP patient population.

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Section: Resultsmentioning

confidence: 99%

Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia

et al. 2010

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“…Twelve different SPG4 mutations and four exon deletions were identified in 17 cases (Table 1). Seven of the mutations and two of the deletions have not been described previously (GeneClinics and HGMD databases), whilst the other five mutations and two exon deletions are known [12,13,15,23–26]. Eleven mutations and the four deletions were located in coding areas of the gene and there was one splice mutation.…”

Section: Resultsmentioning

confidence: 99%

Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia

Erichsen

Inderhaug

Mattingsdal

et al. 2007

Euro J of Neurology

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To establish the phenotypic variation and frequency of SPAST mutations or deletions in Norwegian patients with hereditary spastic paraplegia (HSP), we examined 59 unrelated patients with HSP and screened for DNA point mutations and microdeletions in SPG4. Forty-one had a familial history, 35 had a clear dominant inheritance, six had other affected sibs and 18 were sporadic. We found 12 mutations in SPG4, seven of them novel, and four different heterozygous exon deletions, two of them novel. Mutations were found in 16 families showing autosomal dominant (AD) inheritance, and in one sporadic case. In two non-SPG4 families the S44L polymorphism/modifier was found in both affected and unaffected individuals. This is the first study of Norwegian patients with HSP since the 1970s, and the first report on SPG4 in Norway. Our results show that SPG4 mutations and deletions are a significant cause of HSP in our population and warrant SPG4 screening in AD families and selected sporadic cases.

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“…9,30 -32 In family FSP-748, an abnormal profile in exon 11 revealed the presence of the c.1376G4C/p.Arg459Thr missense mutation, which has been previously reported in another HSP family. 33 A novel missense mutation in exon 11, c.1324G4A/p.Glu442Lys, was identified in the proband of family AAR-392. Glutamic acid at position 442 is located in the AAA cassette of spastin and is conserved in mammals as well as in Drosophila and Fugu.…”

Section: Clinical Featuresmentioning

confidence: 99%

Mental deficiency in three families with SPG4 spastic paraplegia

et al. 2007

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Mutations and deletions in the SPG4 gene are responsible for up to 40% of autosomal dominant hereditary spastic paraplegia (HSP). Patients have pyramidal signs in the lower limbs and some present additional features including cognitive impairment such as executive dysfunction or subcortical dementia. We report 13 patients from three SPG4 families, who had spastic paraplegia associated with mental retardation (n=1), extensive social dependence (n=10), or isolated psychomotor delay (n=2). In family FSP-698, 10 affected individuals had both HSP and mental deficiency leading to social dependence in 9 and institutionalization in 5. The mean age at onset of spastic paraplegia was 11+/-20 years, ranging from 1 to 51 years. This phenotype segregated either with a novel p.Glu442Lys mutation or the two previously described p.Arg459Thr and p.Arg499Cys substitutions in the SPG4 gene. Since two of these mutations were previously reported in families with a pure form of the disease, another genetic factor linked to SPG4 could be responsible for this complex phenotype.

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Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation analysis

Cited by 19 publications

References 10 publications

Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia

Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia

Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia

Mental deficiency in three families with SPG4 spastic paraplegia

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