Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy

P. Ostergaard; M.A. Simpson; A. Mendola; P. Vasudevan; F.C. Connell; A. van Impel; A.T. Moore; B.L. Loeys; A. Ghalamkarpour; A. Onoufriadis; I. Martinez-Corral; S. Devery; J.G. Leroy; L. van Laer; A. Singer; M.G. Bialer; M. McEntagart; O. Quarrell; G. Brice; R.C. Trembath; S. Schulte-Merker; T. Makinen; M. Vikkula; P.S. Mortimer; S. Mansour; S. Jeffery

doi:10.1016/j.ajhg.2011.12.018

Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy

P. Ostergaard, M.A. Simpson, A. Mendola, P. Vasudevan, F.C. Connell, A. van Impel, A.T. Moore, B.L. Loeys, A. Ghalamkarpour, A. Onoufriadis, I. Martinez-Corral, S. Devery, J.G. Leroy, L. van Laer, A. Singer, M.G. Bialer, M. McEntagart, O. Quarrell, G. Brice, R.C. TrembathS. Schulte-Merker, T. Makinen, M. Vikkula, P.S. Mortimer, S. Mansour, S. Jeffery

Hubrecht Institute

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144 Citaten (Scopus)

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We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.

Originele taal-2	Engels
Pagina's (van-tot)	356-362
Tijdschrift	American Journal of Human Genetics
Volume	90
Nummer van het tijdschrift	2
DOI's	https://doi.org/10.1016/j.ajhg.2011.12.018
Status	Gepubliceerd - 2012

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10.1016/j.ajhg.2011.12.018

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Ostergaard, P., Simpson, M. A., Mendola, A., Vasudevan, P., Connell, F. C., van Impel, A., Moore, A. T., Loeys, B. L., Ghalamkarpour, A., Onoufriadis, A., Martinez-Corral, I., Devery, S., Leroy, J. G., van Laer, L., Singer, A., Bialer, M. G., McEntagart, M., Quarrell, O., Brice, G., ... Jeffery, S. (2012). Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. American Journal of Human Genetics, 90(2), 356-362. https://doi.org/10.1016/j.ajhg.2011.12.018

@article{87507ae6e1ed483096bdf4e55806e3be,

title = "Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy",

abstract = "We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.",

author = "P. Ostergaard and M.A. Simpson and A. Mendola and P. Vasudevan and F.C. Connell and {van Impel}, A. and A.T. Moore and B.L. Loeys and A. Ghalamkarpour and A. Onoufriadis and I. Martinez-Corral and S. Devery and J.G. Leroy and {van Laer}, L. and A. Singer and M.G. Bialer and M. McEntagart and O. Quarrell and G. Brice and R.C. Trembath and S. Schulte-Merker and T. Makinen and M. Vikkula and P.S. Mortimer and S. Mansour and S. Jeffery",

note = "Reporting year: 2012",

year = "2012",

doi = "10.1016/j.ajhg.2011.12.018",

language = "English",

volume = "90",

pages = "356--362",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

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Ostergaard, P, Simpson, MA, Mendola, A, Vasudevan, P, Connell, FC, van Impel, A, Moore, AT, Loeys, BL, Ghalamkarpour, A, Onoufriadis, A, Martinez-Corral, I, Devery, S, Leroy, JG, van Laer, L, Singer, A, Bialer, MG, McEntagart, M, Quarrell, O, Brice, G, Trembath, RC, Schulte-Merker, S, Makinen, T, Vikkula, M, Mortimer, PS, Mansour, S & Jeffery, S 2012, 'Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy', American Journal of Human Genetics, vol. 90, nr. 2, blz. 356-362. https://doi.org/10.1016/j.ajhg.2011.12.018

Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. / Ostergaard, P.; Simpson, M.A.; Mendola, A. et al.
In: American Journal of Human Genetics, Vol. 90, Nr. 2, 2012, blz. 356-362.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

TY - JOUR

T1 - Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy

AU - Ostergaard, P.

AU - Simpson, M.A.

AU - Mendola, A.

AU - Vasudevan, P.

AU - Connell, F.C.

AU - van Impel, A.

AU - Moore, A.T.

AU - Loeys, B.L.

AU - Ghalamkarpour, A.

AU - Onoufriadis, A.

AU - Martinez-Corral, I.

AU - Devery, S.

AU - Leroy, J.G.

AU - van Laer, L.

AU - Singer, A.

AU - Bialer, M.G.

AU - McEntagart, M.

AU - Quarrell, O.

AU - Brice, G.

AU - Trembath, R.C.

AU - Schulte-Merker, S.

AU - Makinen, T.

AU - Vikkula, M.

AU - Mortimer, P.S.

AU - Mansour, S.

AU - Jeffery, S.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

N2 - We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.

AB - We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.

U2 - 10.1016/j.ajhg.2011.12.018

DO - 10.1016/j.ajhg.2011.12.018

M3 - Article

SN - 0002-9297

VL - 90

SP - 356

EP - 362

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 2

ER -

Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy

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