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 Dürr; Giovanni Stevanin; Leslie G. Biesecker; John Accardi; Dennis M D Landis; William A. Gahl; Bryan J. Traynor; Wilson Marques; Stephan Züchner; Craig Blackstone; Kenneth H. Fischbeck; Barrington G. Burnett

doi:10.1002/humu.22378

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 Züchner, Craig Blackstone, Kenneth H. Fischbeck, Barrington G. Burnett

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

73 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 language	English
Pages (from-to)	1357-1360
Number of pages	4
Journal	Human mutation
Volume	34
Issue number	10
DOIs	https://doi.org/10.1002/humu.22378
Publication status	Published - Oct 2013
Externally published	Yes

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Landouré, G., Zhu, P. P., Lourenço, C. M., Johnson, J. O., Toro, C., Bricceno, K. V., Rinaldi, C., Meilleur, K. G., Sangaré, M., Diallo, O., Pierson, T. M., Ishiura, H., Tsuji, S., Hein, N., Fink, J. K., Stoll, M., Nicholson, G., Gonzalez, M. A., Speziani, F., ... 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

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 ; Züchner, Stephan ; 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.

@article{4655fda3fbac43d69831f0b26d4854a8,

title = "Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12",

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.",

author = "Guida Landour{\'e} and Zhu, {Peng Peng} and Louren{\c c}o, {Charles M.} and Johnson, {Janel O.} and Camilo Toro and Bricceno, {Katherine V.} and Carlo Rinaldi and Meilleur, {Katherine G.} and Modibo Sangar{\'e} and Oumarou Diallo and Pierson, {Tyler M.} and Hiroyuki Ishiura and Shoji Tsuji and Nichole Hein and Fink, {John K.} and Marion Stoll and Garth Nicholson and Gonzalez, {Michael A.} and Fiorella Speziani and Alexandra D{\"u}rr and Giovanni Stevanin and Biesecker, {Leslie G.} and John Accardi and Landis, {Dennis M D} and Gahl, {William A.} and Traynor, {Bryan J.} and Wilson Marques and Stephan Z{\"u}chner and Craig Blackstone and Fischbeck, {Kenneth H.} and Burnett, {Barrington G.}",

year = "2013",

month = oct,

doi = "10.1002/humu.22378",

language = "English",

volume = "34",

pages = "1357--1360",

journal = "Human mutation",

issn = "1059-7794",

publisher = "Wiley-Blackwell, Wiley",

number = "10",

}

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, Züchner, S, 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

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; Züchner, Stephan; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

In: Human mutation, Vol. 34, No. 10, 10.2013, p. 1357-1360.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Hereditary spastic paraplegia Type 43 (SPG43) is caused by mutation in C19orf12

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 - Züchner, Stephan

AU - Blackstone, Craig

AU - Fischbeck, Kenneth H.

AU - Burnett, Barrington G.

PY - 2013/10

Y1 - 2013/10

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.

UR - http://www.scopus.com/inward/record.url?scp=84884535149&partnerID=8YFLogxK

U2 - 10.1002/humu.22378

DO - 10.1002/humu.22378

M3 - Article

C2 - 23857908

AN - SCOPUS:84884535149

VL - 34

SP - 1357

EP - 1360

JO - Human mutation

JF - Human mutation

SN - 1059-7794

IS - 10

ER -

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

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