Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3

J.C. Sim; T. Scerri; M. Fanjul-Fernández; J.R. Riseley; G. Gillies; K. Pope; H. Van Roozendaal; Julian Heng; S.A. Mandelstam; G. Mcgillivray; D. Macgregor; L. Kannan; W. Maixner; A.S. Harvey; D.J. Amor; M.B. Delatycki; P.B. Crino; M. Bahlo; P.J. Lockhart; R.J. Leventer

doi:10.1002/ana.24502

Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3

J.C. Sim, T. Scerri, M. Fanjul-Fernández, J.R. Riseley, G. Gillies, K. Pope, H. Van Roozendaal, Julian Heng, S.A. Mandelstam, G. Mcgillivray, D. Macgregor, L. Kannan, W. Maixner, A.S. Harvey, D.J. Amor, M.B. Delatycki, P.B. Crino, M. Bahlo, P.J. Lockhart, R.J. Leventer

UWA Centre for Medical Research (affiliated with the Harry Perkins Institute of Medical Research)

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

127 Citations (Scopus)

Abstract

© 2015 American Neurological Association. We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole-exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator-like 3 (NPRL3). NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway. Immunostaining of resected brain tissue demonstrated mammalian target of rapamycin activation. Screening of 52 unrelated individuals with FCD identified 2 additional patients with FCDIIa and germline NPRL3 mutations. Similar to DEPDC5, NPRL3 mutations may be considered as causal variants in patients with FCD or magnetic resonance imaging-negative focal epilepsy.

Original language	English
Pages (from-to)	132-137
Number of pages	6
Journal	Annals of Neurology
Volume	79
Issue number	1
Early online date	12 Dec 2015
DOIs	https://doi.org/10.1002/ana.24502
Publication status	Published - 1 Jan 2016

Access to Document

10.1002/ana.24502

Cite this

Sim, J. C., Scerri, T., Fanjul-Fernández, M., Riseley, J. R., Gillies, G., Pope, K., Van Roozendaal, H., Heng, J., Mandelstam, S. A., Mcgillivray, G., Macgregor, D., Kannan, L., Maixner, W., Harvey, A. S., Amor, D. J., Delatycki, M. B., Crino, P. B., Bahlo, M., Lockhart, P. J., & Leventer, R. J. (2016). Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3. Annals of Neurology, 79(1), 132-137. https://doi.org/10.1002/ana.24502

@article{d4ea4862f5d242928f2eb4403e6bd138,

title = "Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3",

abstract = "{\textcopyright} 2015 American Neurological Association. We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole-exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator-like 3 (NPRL3). NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway. Immunostaining of resected brain tissue demonstrated mammalian target of rapamycin activation. Screening of 52 unrelated individuals with FCD identified 2 additional patients with FCDIIa and germline NPRL3 mutations. Similar to DEPDC5, NPRL3 mutations may be considered as causal variants in patients with FCD or magnetic resonance imaging-negative focal epilepsy.",

author = "J.C. Sim and T. Scerri and M. Fanjul-Fern{\'a}ndez and J.R. Riseley and G. Gillies and K. Pope and {Van Roozendaal}, H. and Julian Heng and S.A. Mandelstam and G. Mcgillivray and D. Macgregor and L. Kannan and W. Maixner and A.S. Harvey and D.J. Amor and M.B. Delatycki and P.B. Crino and M. Bahlo and P.J. Lockhart and R.J. Leventer",

year = "2016",

month = jan,

day = "1",

doi = "10.1002/ana.24502",

language = "English",

volume = "79",

pages = "132--137",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "Wiley-Blackwell",

number = "1",

}

Sim, JC, Scerri, T, Fanjul-Fernández, M, Riseley, JR, Gillies, G, Pope, K, Van Roozendaal, H, Heng, J, Mandelstam, SA, Mcgillivray, G, Macgregor, D, Kannan, L, Maixner, W, Harvey, AS, Amor, DJ, Delatycki, MB, Crino, PB, Bahlo, M, Lockhart, PJ & Leventer, RJ 2016, 'Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3', Annals of Neurology, vol. 79, no. 1, pp. 132-137. https://doi.org/10.1002/ana.24502

TY - JOUR

T1 - Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3

AU - Sim, J.C.

AU - Scerri, T.

AU - Fanjul-Fernández, M.

AU - Riseley, J.R.

AU - Gillies, G.

AU - Pope, K.

AU - Van Roozendaal, H.

AU - Heng, Julian

AU - Mandelstam, S.A.

AU - Mcgillivray, G.

AU - Macgregor, D.

AU - Kannan, L.

AU - Maixner, W.

AU - Harvey, A.S.

AU - Amor, D.J.

AU - Delatycki, M.B.

AU - Crino, P.B.

AU - Bahlo, M.

AU - Lockhart, P.J.

AU - Leventer, R.J.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - © 2015 American Neurological Association. We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole-exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator-like 3 (NPRL3). NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway. Immunostaining of resected brain tissue demonstrated mammalian target of rapamycin activation. Screening of 52 unrelated individuals with FCD identified 2 additional patients with FCDIIa and germline NPRL3 mutations. Similar to DEPDC5, NPRL3 mutations may be considered as causal variants in patients with FCD or magnetic resonance imaging-negative focal epilepsy.

AB - © 2015 American Neurological Association. We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole-exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator-like 3 (NPRL3). NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway. Immunostaining of resected brain tissue demonstrated mammalian target of rapamycin activation. Screening of 52 unrelated individuals with FCD identified 2 additional patients with FCDIIa and germline NPRL3 mutations. Similar to DEPDC5, NPRL3 mutations may be considered as causal variants in patients with FCD or magnetic resonance imaging-negative focal epilepsy.

U2 - 10.1002/ana.24502

DO - 10.1002/ana.24502

M3 - Article

C2 - 26285051

SN - 0364-5134

VL - 79

SP - 132

EP - 137

JO - Annals of Neurology

JF - Annals of Neurology

IS - 1

ER -

Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3

Abstract

Access to Document

Fingerprint

Cite this