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De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.

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De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. / Rivière, Jean-Baptiste; Mirzaa, Ghayda M; O'Roak, Brian J; Beddaoui, Margaret; Alcantara, Diana; Conway, Robert L; St-Onge, Judith; Schwartzentruber, Jeremy A; Gripp, Karen W; Nikkel, Sarah M; Worthylake, Thea; Sullivan, Christopher T; Ward, Thomas R; Butler, Hailly E; Kramer, Nancy A; Albrecht, Beate; Armour, Christine M; Armstrong, Linlea; Caluseriu, Oana; Cytrynbaum, Cheryl; Drolet, Beth A; Innes, A Micheil; Lauzon, Julie L; Lin, Angela E; Mancini, Grazia M S; Meschino, Wendy S; Reggin, James D; Saggar, Anand K; Lerman-Sagie, Tally; Uyanik, Gökhan; Weksberg, Rosanna; Zirn, Birgit; Beaulieu, Chandree L; Consortium, Finding Of Rare Disease Genes Canada; Majewski, Jacek; Bulman, Dennis E; O'Driscoll, Mark; Shendure, Jay; Graham, John M; Boycott, Kym M; Dobyns, William B.

In: NAT GENET, Vol. 44, No. 8, 8, 2012, p. 934-940.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rivière, J-B, Mirzaa, GM, O'Roak, BJ, Beddaoui, M, Alcantara, D, Conway, RL, St-Onge, J, Schwartzentruber, JA, Gripp, KW, Nikkel, SM, Worthylake, T, Sullivan, CT, Ward, TR, Butler, HE, Kramer, NA, Albrecht, B, Armour, CM, Armstrong, L, Caluseriu, O, Cytrynbaum, C, Drolet, BA, Innes, AM, Lauzon, JL, Lin, AE, Mancini, GMS, Meschino, WS, Reggin, JD, Saggar, AK, Lerman-Sagie, T, Uyanik, G, Weksberg, R, Zirn, B, Beaulieu, CL, Consortium, FORDGC, Majewski, J, Bulman, DE, O'Driscoll, M, Shendure, J, Graham, JM, Boycott, KM & Dobyns, WB 2012, 'De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.', NAT GENET, vol. 44, no. 8, 8, pp. 934-940. <http://www.ncbi.nlm.nih.gov/pubmed/22729224?dopt=Citation>

APA

Rivière, J-B., Mirzaa, G. M., O'Roak, B. J., Beddaoui, M., Alcantara, D., Conway, R. L., St-Onge, J., Schwartzentruber, J. A., Gripp, K. W., Nikkel, S. M., Worthylake, T., Sullivan, C. T., Ward, T. R., Butler, H. E., Kramer, N. A., Albrecht, B., Armour, C. M., Armstrong, L., Caluseriu, O., ... Dobyns, W. B. (2012). De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. NAT GENET, 44(8), 934-940. [8]. http://www.ncbi.nlm.nih.gov/pubmed/22729224?dopt=Citation

Vancouver

Rivière J-B, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. NAT GENET. 2012;44(8):934-940. 8.

Bibtex

@article{99ab8731c72040b1a17a0fa25b1b1809,
title = "De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.",
abstract = "Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.",
keywords = "Humans, Mutation, Missense, Syndrome, *Mutation, Germ-Line Mutation, Exome, Hydrocephalus/enzymology/genetics/pathology, Macrocephaly/enzymology/*genetics/pathology, Malformations of Cortical Development/enzymology/*genetics/pathology, Phosphatidylinositol 3-Kinases/*genetics, Proto-Oncogene Proteins c-akt/*genetics, Humans, Mutation, Missense, Syndrome, *Mutation, Germ-Line Mutation, Exome, Hydrocephalus/enzymology/genetics/pathology, Macrocephaly/enzymology/*genetics/pathology, Malformations of Cortical Development/enzymology/*genetics/pathology, Phosphatidylinositol 3-Kinases/*genetics, Proto-Oncogene Proteins c-akt/*genetics",
author = "Jean-Baptiste Rivi{\`e}re and Mirzaa, {Ghayda M} and O'Roak, {Brian J} and Margaret Beddaoui and Diana Alcantara and Conway, {Robert L} and Judith St-Onge and Schwartzentruber, {Jeremy A} and Gripp, {Karen W} and Nikkel, {Sarah M} and Thea Worthylake and Sullivan, {Christopher T} and Ward, {Thomas R} and Butler, {Hailly E} and Kramer, {Nancy A} and Beate Albrecht and Armour, {Christine M} and Linlea Armstrong and Oana Caluseriu and Cheryl Cytrynbaum and Drolet, {Beth A} and Innes, {A Micheil} and Lauzon, {Julie L} and Lin, {Angela E} and Mancini, {Grazia M S} and Meschino, {Wendy S} and Reggin, {James D} and Saggar, {Anand K} and Tally Lerman-Sagie and G{\"o}khan Uyanik and Rosanna Weksberg and Birgit Zirn and Beaulieu, {Chandree L} and Consortium, {Finding Of Rare Disease Genes Canada} and Jacek Majewski and Bulman, {Dennis E} and Mark O'Driscoll and Jay Shendure and Graham, {John M} and Boycott, {Kym M} and Dobyns, {William B}",
year = "2012",
language = "English",
volume = "44",
pages = "934--940",
journal = "NAT GENET",
issn = "1061-4036",
publisher = "NATURE PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.

AU - Rivière, Jean-Baptiste

AU - Mirzaa, Ghayda M

AU - O'Roak, Brian J

AU - Beddaoui, Margaret

AU - Alcantara, Diana

AU - Conway, Robert L

AU - St-Onge, Judith

AU - Schwartzentruber, Jeremy A

AU - Gripp, Karen W

AU - Nikkel, Sarah M

AU - Worthylake, Thea

AU - Sullivan, Christopher T

AU - Ward, Thomas R

AU - Butler, Hailly E

AU - Kramer, Nancy A

AU - Albrecht, Beate

AU - Armour, Christine M

AU - Armstrong, Linlea

AU - Caluseriu, Oana

AU - Cytrynbaum, Cheryl

AU - Drolet, Beth A

AU - Innes, A Micheil

AU - Lauzon, Julie L

AU - Lin, Angela E

AU - Mancini, Grazia M S

AU - Meschino, Wendy S

AU - Reggin, James D

AU - Saggar, Anand K

AU - Lerman-Sagie, Tally

AU - Uyanik, Gökhan

AU - Weksberg, Rosanna

AU - Zirn, Birgit

AU - Beaulieu, Chandree L

AU - Consortium, Finding Of Rare Disease Genes Canada

AU - Majewski, Jacek

AU - Bulman, Dennis E

AU - O'Driscoll, Mark

AU - Shendure, Jay

AU - Graham, John M

AU - Boycott, Kym M

AU - Dobyns, William B

PY - 2012

Y1 - 2012

N2 - Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.

AB - Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.

KW - Humans

KW - Mutation, Missense

KW - Syndrome

KW - Mutation

KW - Germ-Line Mutation

KW - Exome

KW - Hydrocephalus/enzymology/genetics/pathology

KW - Macrocephaly/enzymology/genetics/pathology

KW - Malformations of Cortical Development/enzymology/genetics/pathology

KW - Phosphatidylinositol 3-Kinases/genetics

KW - Proto-Oncogene Proteins c-akt/genetics

KW - Humans

KW - Mutation, Missense

KW - Syndrome

KW - Mutation

KW - Germ-Line Mutation

KW - Exome

KW - Hydrocephalus/enzymology/genetics/pathology

KW - Macrocephaly/enzymology/genetics/pathology

KW - Malformations of Cortical Development/enzymology/genetics/pathology

KW - Phosphatidylinositol 3-Kinases/genetics

KW - Proto-Oncogene Proteins c-akt/genetics

M3 - SCORING: Journal article

VL - 44

SP - 934

EP - 940

JO - NAT GENET

JF - NAT GENET

SN - 1061-4036

IS - 8

M1 - 8

ER -