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Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy

Ostergaard, P; Simpson, MA; Mendola, A; Vasudevan, P; Connell, FC; van Impel, A; Moore, AT; Loeys, BL; Ghalamkarpour, A; Onoufriadis, A; et al. 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, 90 (2). 356 - 362. ISSN 0002-9297 https://doi.org/10.1016/j.ajhg.2011.12.018
SGUL Authors: Jeffery, Stephen Mortimer, Peter Sydney Ostergaard, Pia Mansour, Sahar McEntagart, Meriel Brice, Glen Worthington

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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.

Item Type: Article
Additional Information: Accepted version made available by permission of publisher, Cell Press.
Keywords: Abnormalities, Multiple, Cholestasis, Cohort Studies, Congenital Abnormalities, Exome, Facies, Female, Heterozygote, Humans, Kinesin, Lymphedema, Male, Microcephaly, Mutation, Pedigree, Phenotype, Retinal Dysplasia, Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENETICS & HEREDITY, OF-THE-LITERATURE, MITOTIC SPINDLE, MOTOR PROTEIN, KINESIN EG5, DYSPLASIA, Genetics & Heredity, 06 Biological Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: AMERICAN JOURNAL OF HUMAN GENETICS
ISSN: 0002-9297
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Dates:
DateEvent
10 February 2012Published
Web of Science ID: WOS:000300742200018
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URI: https://openaccess.sgul.ac.uk/id/eprint/107099
Publisher's version: https://doi.org/10.1016/j.ajhg.2011.12.018

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