Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12

Guida Landouré, Peng Peng Zhu, Charles M. Lourenço, Janel O. Johnson, Camilo Toro, Katherine V. Bricceno, Carlo Rinaldi, Katherine G. Meilleur, Modibo Sangaré, Oumarou Diallo, Tyler M. Pierson, Hiroyuki Ishiura, Shoji Tsuji, Nichole Hein, John K. Fink, Marion Stoll, Garth Nicholson, Michael A. Gonzalez, Fiorella Speziani, Alexandra DürrGiovanni Stevanin, Leslie G. Biesecker, John Accardi, Dennis M D Landis, William A. Gahl, Bryan J. Traynor, Wilson Marques, Stephan L Zuchner, Craig Blackstone, Kenneth H. Fischbeck, Barrington G. Burnett

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.

Original languageEnglish
Pages (from-to)1357-1360
Number of pages4
JournalHuman Mutation
Volume34
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Hereditary Spastic Paraplegia
Paraplegia
Mutation
Exome
Missense Mutation
Haplotypes
Neurodegeneration with brain iron accumulation (NBIA)
Siblings
Nucleotides
Iron
Magnetic Resonance Imaging
Brain
Genes

Keywords

  • C19orf12
  • Hereditary spastic paraplegia
  • NBIA
  • SPG43

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Landouré, G., Zhu, P. P., Lourenço, C. M., Johnson, J. O., Toro, C., Bricceno, K. V., ... Burnett, B. G. (2013). Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12. Human Mutation, 34(10), 1357-1360. https://doi.org/10.1002/humu.22378

Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12. / Landouré, Guida; Zhu, Peng Peng; Lourenço, Charles M.; Johnson, Janel O.; Toro, Camilo; Bricceno, Katherine V.; Rinaldi, Carlo; Meilleur, Katherine G.; Sangaré, Modibo; Diallo, Oumarou; Pierson, Tyler M.; Ishiura, Hiroyuki; Tsuji, Shoji; Hein, Nichole; Fink, John K.; Stoll, Marion; Nicholson, Garth; Gonzalez, Michael A.; Speziani, Fiorella; Dürr, Alexandra; Stevanin, Giovanni; Biesecker, Leslie G.; Accardi, John; Landis, Dennis M D; Gahl, William A.; Traynor, Bryan J.; Marques, Wilson; Zuchner, Stephan L; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

In: Human Mutation, Vol. 34, No. 10, 01.10.2013, p. 1357-1360.

Research output: Contribution to journalArticle

Landouré, G, Zhu, PP, Lourenço, CM, Johnson, JO, Toro, C, Bricceno, KV, Rinaldi, C, Meilleur, KG, Sangaré, M, Diallo, O, Pierson, TM, Ishiura, H, Tsuji, S, Hein, N, Fink, JK, Stoll, M, Nicholson, G, Gonzalez, MA, Speziani, F, Dürr, A, Stevanin, G, Biesecker, LG, Accardi, J, Landis, DMD, Gahl, WA, Traynor, BJ, Marques, W, Zuchner, SL, Blackstone, C, Fischbeck, KH & Burnett, BG 2013, 'Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12', Human Mutation, vol. 34, no. 10, pp. 1357-1360. https://doi.org/10.1002/humu.22378
Landouré G, Zhu PP, Lourenço CM, Johnson JO, Toro C, Bricceno KV et al. Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12. Human Mutation. 2013 Oct 1;34(10):1357-1360. https://doi.org/10.1002/humu.22378
Landouré, Guida ; Zhu, Peng Peng ; Lourenço, Charles M. ; Johnson, Janel O. ; Toro, Camilo ; Bricceno, Katherine V. ; Rinaldi, Carlo ; Meilleur, Katherine G. ; Sangaré, Modibo ; Diallo, Oumarou ; Pierson, Tyler M. ; Ishiura, Hiroyuki ; Tsuji, Shoji ; Hein, Nichole ; Fink, John K. ; Stoll, Marion ; Nicholson, Garth ; Gonzalez, Michael A. ; Speziani, Fiorella ; Dürr, Alexandra ; Stevanin, Giovanni ; Biesecker, Leslie G. ; Accardi, John ; Landis, Dennis M D ; Gahl, William A. ; Traynor, Bryan J. ; Marques, Wilson ; Zuchner, Stephan L ; Blackstone, Craig ; Fischbeck, Kenneth H. ; Burnett, Barrington G. / Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12. In: Human Mutation. 2013 ; Vol. 34, No. 10. pp. 1357-1360.
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abstract = "We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.",
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AU - Landouré, Guida

AU - Zhu, Peng Peng

AU - Lourenço, Charles M.

AU - Johnson, Janel O.

AU - Toro, Camilo

AU - Bricceno, Katherine V.

AU - Rinaldi, Carlo

AU - Meilleur, Katherine G.

AU - Sangaré, Modibo

AU - Diallo, Oumarou

AU - Pierson, Tyler M.

AU - Ishiura, Hiroyuki

AU - Tsuji, Shoji

AU - Hein, Nichole

AU - Fink, John K.

AU - Stoll, Marion

AU - Nicholson, Garth

AU - Gonzalez, Michael A.

AU - Speziani, Fiorella

AU - Dürr, Alexandra

AU - Stevanin, Giovanni

AU - Biesecker, Leslie G.

AU - Accardi, John

AU - Landis, Dennis M D

AU - Gahl, William A.

AU - Traynor, Bryan J.

AU - Marques, Wilson

AU - Zuchner, Stephan L

AU - Blackstone, Craig

AU - Fischbeck, Kenneth H.

AU - Burnett, Barrington G.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.

AB - We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.

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KW - Hereditary spastic paraplegia

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KW - SPG43

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