Posted by: patoconnor | February 13, 2012

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

Jan 2012

Ostergaard PSimpson MAMendola AVasudevan PConnell FCvan Impel AMoore ATLoeys BLGhalamkarpour A,Onoufriadis AMartinez-Corral IDevery SLeroy JGvan Laer LSinger ABialer MGMcEntagart MQuarrell OBrice G,Trembath RCSchulte-Merker SMakinen TVikkula MMortimer PSMansour SJeffery S.

Source

Medical Genetics Unit, Biomedical Sciences, St. George’s University of London, London SW17 0RE, UK.

Abstract

We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated withlymphedema 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.

Cell Press


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Categories

%d bloggers like this: