title: Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations.
abstract: Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing.
authors.affiliation: Clinical Genetics Department, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Jones
authors.affiliation: Human Genetics Research Centre, Biomedical Sciences, St George's University of London, London, UK.
authors.forename: Pia
authors.initials: P
authors.lastname: Ostergaard
authors.affiliation: Moorfields Eye Hospital, London, UK.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: Clinical Genetics Department, Guys and St Thomas' Hospital, London, UK.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Connell
authors.affiliation: Clinical Genetics Department, Birmingham Women's Hospital, Birmingham, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.affiliation: Sheffield Clinical Genetics Department, Sheffield Children's NHS Trust, Sheffield, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Quarrell
authors.affiliation: Clinical Genetics Department, Kennedy Galton Centre, North West London Hospitals NHS Trust, London, UK.
authors.forename: Angela F
authors.initials: AF
authors.lastname: Brady
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Spier
authors.affiliation: Department of Medical Genetics, Dr Behçet Uz Children's Hospital, Izmir, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Hazan
authors.affiliation: Serviço de Genética Médica, Hospital Santa Maria, Lisbon, Portugal.
authors.forename: Oana
authors.initials: O
authors.lastname: Moldovan
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Dusiburg-Essen, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Dusiburg-Essen, Essen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mikat
authors.affiliation: Service de Genetique Clinique, Hôpital Jeanne de Flandre, Université Lille Nord de France, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
authors.affiliation: Department of Medical Genetics, Arnaud de Villeneuve's Hospital, Montpellier, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Coubes
authors.affiliation: Children's Hospital (formerly Greenwood Genetic Center, Greenwood, SC, USA), Greenville, SC, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Saul
authors.affiliation: South West Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.
authors.forename: Glen
authors.initials: G
authors.lastname: Brice
authors.affiliation: Department of Clinical Sciences, St George's University of London, London, UK.
authors.forename: Kristiana
authors.initials: K
authors.lastname: Gordon
authors.affiliation: Human Genetics Research Centre, Biomedical Sciences, St George's University of London, London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Jeffery
authors.affiliation: Department of Clinical Sciences, St George's University of London, London, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Mortimer
authors.affiliation: Clinical Genetics Department, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: Pradeep C
authors.initials: PC
authors.lastname: Vasudevan
authors.affiliation: South West Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
mesh_terms: D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D016547:Kinesins / Q000235:genetics*; D008209:Lymphedema / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D019683:Penetrance; D010641:Phenotype; D012164:Retinal Diseases / Q000235:genetics*
chemical_list: C470243:KIF11 protein, human; D016547:Kinesins