Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia

Kirsten Svenstrup; Peter Bross; Pernille Koefoed; Lena E Hjermind; Hans Eiberg; A Peter Born; John Vissing; Jesper Gyllenborg; Anne Nørremølle; Lis Hasholt; Jørgen E Nielsen; Kirsten Svenstrup; Peter Bross; Pernille Koefoed; Lena E Hjermind; Hans Eiberg; A Peter Born; John Vissing; Jesper Gyllenborg; Anne Nørremølle; Lis Hasholt; Jørgen E Nielsen

doi:10.1016/j.jns.2009.04.024

Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia

Kirsten Svenstrup, Peter Bross, Pernille Koefoed, Lena E Hjermind, Hans Eiberg, A Peter Born, John Vissing, Jesper Gyllenborg, Anne Nørremølle, Lis Hasholt, Jørgen E Nielsen, Kirsten Svenstrup, Peter Bross, Pernille Koefoed, Lena E Hjermind, Hans Eiberg, A Peter Born, John Vissing, Jesper Gyllenborg, Anne NørremølleLis Hasholt, Jørgen E Nielsen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

18 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009

Originalsprog	Engelsk
Tidsskrift	Journal of the Neurological Sciences
Vol/bind	284
Udgave nummer	1-2
Sider (fra-til)	90-5
Antal sider	5
ISSN	0022-510X
DOI	https://doi.org/10.1016/j.jns.2009.04.024 https://doi.org/10.1016/j.jns.2009.04.024
Status	Udgivet - 2009

Bibliografisk note

Keywords: Adenosine Triphosphatases; Amino Acid Motifs; Amino Acid Substitution; Cells, Cultured; Chaperonin 60; DNA Mutational Analysis; Denmark; Female; Fibroblasts; GTP Phosphohydrolases; Genetic Heterogeneity; Genetic Variation; Genotype; Humans; Male; Pedigree; Phenotype; Polymorphism, Single Nucleotide; RNA Splice Sites; Sequence Analysis, DNA; Sequence Deletion; Spastic Paraplegia, Hereditary

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Citationsformater

Svenstrup, K., Bross, P., Koefoed, P., Hjermind, L. E., Eiberg, H., Born, A. P., Vissing, J., Gyllenborg, J., Nørremølle, A., Hasholt, L., Nielsen, J. E., Svenstrup, K., Bross, P., Koefoed, P., Hjermind, L. E., Eiberg, H., Born, A. P., Vissing, J., Gyllenborg, J., ... Nielsen, J. E. (2009). Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia. Journal of the Neurological Sciences, 284(1-2), 90-5. https://doi.org/10.1016/j.jns.2009.04.024, https://doi.org/10.1016/j.jns.2009.04.024

Svenstrup, K, Bross, P, Koefoed, P, Hjermind, LE, Eiberg, H, Born, AP, Vissing, J, Gyllenborg, J, Nørremølle, A , Hasholt, L , Nielsen, JE, Svenstrup, K, Bross, P, Koefoed, P, Hjermind, LE, Eiberg, H, Born, AP, Vissing, J, Gyllenborg, J, Nørremølle, A, Hasholt, L & Nielsen, JE 2009, 'Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia', Journal of the Neurological Sciences, bind 284, nr. 1-2, s. 90-5. https://doi.org/10.1016/j.jns.2009.04.024, https://doi.org/10.1016/j.jns.2009.04.024

@article{cac5ca606a0e11de8bc9000ea68e967b,

title = "Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia",

abstract = "Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and weakness in the lower limbs. The most common forms of autosomal dominant HSP, SPG4 and SPG3, are caused by sequence variants in the SPAST and SPG3A genes, respectively. The pathogenic variants are scattered all over these genes and many variants are unique to a specific family. The phenotype in SPG4 patients can be modified by a variant in SPAST (p.Ser44Leu) and recently, a variant in HSPD1, the gene underlying SPG13, was reported as a second genetic modifier in SPG4 patients. In this study HSP patients were screened for variants in SPG3A, SPAST and HSPD1 in order to identify disease causing variations. SPAST was sequenced in all patients whereas subsets were sequenced in HSPD1 and in selected exons of SPG3A. SPG4 patients and their HSP relatives were genotyped for the modifying variant in HSPD1. We report six new sequence variants in SPAST including a fourth non synonymous sequence variant in exon 1 and two synonymous changes of which one has been found in a HSP patient previously, but never in controls. Of the novel variants in SPAST four were interpreted as disease causing. In addition one new disease causing sequence variant and one non pathogenic non synonymous variant were found in SPG3A. In HSPD1 we identified a sporadic patient homozygote for the potential modifying variation. The effect of the modifying HSPD1 variation was not supported by identification in one SPG4 family.",

author = "Kirsten Svenstrup and Peter Bross and Pernille Koefoed and Hjermind, {Lena E} and Hans Eiberg and Born, {A Peter} and John Vissing and Jesper Gyllenborg and Anne N{\o}rrem{\o}lle and Lis Hasholt and Nielsen, {J{\o}rgen E} and Kirsten Svenstrup and Peter Bross and Pernille Koefoed and Hjermind, {Lena E} and Hans Eiberg and Born, {A Peter} and John Vissing and Jesper Gyllenborg and Anne N{\o}rrem{\o}lle and Lis Hasholt and Nielsen, {J{\o}rgen E}",

note = "Keywords: Adenosine Triphosphatases; Amino Acid Motifs; Amino Acid Substitution; Cells, Cultured; Chaperonin 60; DNA Mutational Analysis; Denmark; Female; Fibroblasts; GTP Phosphohydrolases; Genetic Heterogeneity; Genetic Variation; Genotype; Humans; Male; Pedigree; Phenotype; Polymorphism, Single Nucleotide; RNA Splice Sites; Sequence Analysis, DNA; Sequence Deletion; Spastic Paraplegia, Hereditary",

year = "2009",

doi = "10.1016/j.jns.2009.04.024",

language = "English",

volume = "284",

pages = "90--5",

journal = "Journal of the Neurological Sciences",

issn = "0022-510X",

publisher = "Elsevier",

number = "1-2",

}

TY - JOUR

T1 - Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia

AU - Svenstrup, Kirsten

AU - Bross, Peter

AU - Koefoed, Pernille

AU - Hjermind, Lena E

AU - Eiberg, Hans

AU - Born, A Peter

AU - Vissing, John

AU - Gyllenborg, Jesper

AU - Nørremølle, Anne

AU - Hasholt, Lis

AU - Nielsen, Jørgen E

AU - Svenstrup, Kirsten

AU - Bross, Peter

AU - Koefoed, Pernille

AU - Hjermind, Lena E

AU - Eiberg, Hans

AU - Born, A Peter

AU - Vissing, John

AU - Gyllenborg, Jesper

AU - Nørremølle, Anne

AU - Hasholt, Lis

AU - Nielsen, Jørgen E

N1 - Keywords: Adenosine Triphosphatases; Amino Acid Motifs; Amino Acid Substitution; Cells, Cultured; Chaperonin 60; DNA Mutational Analysis; Denmark; Female; Fibroblasts; GTP Phosphohydrolases; Genetic Heterogeneity; Genetic Variation; Genotype; Humans; Male; Pedigree; Phenotype; Polymorphism, Single Nucleotide; RNA Splice Sites; Sequence Analysis, DNA; Sequence Deletion; Spastic Paraplegia, Hereditary

PY - 2009

Y1 - 2009

N2 - Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and weakness in the lower limbs. The most common forms of autosomal dominant HSP, SPG4 and SPG3, are caused by sequence variants in the SPAST and SPG3A genes, respectively. The pathogenic variants are scattered all over these genes and many variants are unique to a specific family. The phenotype in SPG4 patients can be modified by a variant in SPAST (p.Ser44Leu) and recently, a variant in HSPD1, the gene underlying SPG13, was reported as a second genetic modifier in SPG4 patients. In this study HSP patients were screened for variants in SPG3A, SPAST and HSPD1 in order to identify disease causing variations. SPAST was sequenced in all patients whereas subsets were sequenced in HSPD1 and in selected exons of SPG3A. SPG4 patients and their HSP relatives were genotyped for the modifying variant in HSPD1. We report six new sequence variants in SPAST including a fourth non synonymous sequence variant in exon 1 and two synonymous changes of which one has been found in a HSP patient previously, but never in controls. Of the novel variants in SPAST four were interpreted as disease causing. In addition one new disease causing sequence variant and one non pathogenic non synonymous variant were found in SPG3A. In HSPD1 we identified a sporadic patient homozygote for the potential modifying variation. The effect of the modifying HSPD1 variation was not supported by identification in one SPG4 family.

AB - Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and weakness in the lower limbs. The most common forms of autosomal dominant HSP, SPG4 and SPG3, are caused by sequence variants in the SPAST and SPG3A genes, respectively. The pathogenic variants are scattered all over these genes and many variants are unique to a specific family. The phenotype in SPG4 patients can be modified by a variant in SPAST (p.Ser44Leu) and recently, a variant in HSPD1, the gene underlying SPG13, was reported as a second genetic modifier in SPG4 patients. In this study HSP patients were screened for variants in SPG3A, SPAST and HSPD1 in order to identify disease causing variations. SPAST was sequenced in all patients whereas subsets were sequenced in HSPD1 and in selected exons of SPG3A. SPG4 patients and their HSP relatives were genotyped for the modifying variant in HSPD1. We report six new sequence variants in SPAST including a fourth non synonymous sequence variant in exon 1 and two synonymous changes of which one has been found in a HSP patient previously, but never in controls. Of the novel variants in SPAST four were interpreted as disease causing. In addition one new disease causing sequence variant and one non pathogenic non synonymous variant were found in SPG3A. In HSPD1 we identified a sporadic patient homozygote for the potential modifying variation. The effect of the modifying HSPD1 variation was not supported by identification in one SPG4 family.

U2 - 10.1016/j.jns.2009.04.024

DO - 10.1016/j.jns.2009.04.024

M3 - Journal article

C2 - 19423133

SN - 0022-510X

VL - 284

SP - 90

EP - 95

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

IS - 1-2

ER -