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

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

130 Citaten (Scopus)


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-2Engels
Pagina's (van-tot)356-362
TijdschriftAmerican Journal of Human Genetics
Nummer van het tijdschrift2
StatusGepubliceerd - 2012


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