title: Clinical features associated with CTNNB1 de novo loss of function mutations in ten individuals.
abstract: Loss of function mutations in CTNNB1 have been reported in individuals with intellectual disability [MIM #615075] associated with peripheral spasticity, microcephaly and central hypotonia, suggesting a recognisable phenotype associated with haploinsufficiency for this gene. Trio based whole exome sequencing via the Deciphering Developmental Disorders (DDD) study has identified eleven further individuals with de novo loss of function mutations in CTNNB1. Here we report detailed phenotypic information on ten of these. We confirm the features that have been previously described and further delineate the skin and hair findings, including fair skin and fair and sparse hair with unusual patterning.
authors.affiliation: West of Scotland Clinical Genetics Service, Level 2A Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow, UK. Electronic address: mira.kharbanda@nhs.net.
authors.forename: Mira
authors.initials: M
authors.lastname: Kharbanda
authors.affiliation: West of Scotland Clinical Genetics Service, Level 2A Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: Daniela T
authors.initials: DT
authors.lastname: Pilz
authors.affiliation: Department of Clinical Genetics, St. Michael's Hospital, Bristol, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Tomkins
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Chandler
authors.affiliation: The Portland Hospital for Women and Children, 205-209 Great Portland St, London, W1W 5AH, UK; St George's Hospital, NHS Foundation Trust, Blackshaw Rd, Tooting, SW17 0QT, London, UK.
authors.forename: Anand
authors.initials: A
authors.lastname: Saggar
authors.affiliation: Department of Clinical Genetics, Liverpool Women's NHS Foundation Trust, Liverpool, L8 7SS, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Fryer
authors.affiliation: Department of Clinical Genetics, Liverpool Women's NHS Foundation Trust, Liverpool, L8 7SS, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: McKay
authors.affiliation: Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Pedro
authors.initials: P
authors.lastname: Louro
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Jill Clayton
authors.initials: JC
authors.lastname: Smith
authors.affiliation: Newcastle University - Institute of Genetic Medicine, International Centre for Life Central Parkway, Newcastle Upon Tyne, UK.
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.affiliation: Department of Clinical Genetics, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors.forename: Usha
authors.initials: U
authors.lastname: Kini
authors.affiliation: Department of Clinical Genetics, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: De Burca
authors.affiliation: MRC Human Genetics Unit MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: FitzPatrick
authors.affiliation: West of Scotland Clinical Genetics Service, Level 2A Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: Esther
authors.initials: E
authors.lastname: Kinning
authors.affiliation: DDD Study, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: CTNNB1; Intellectual disability; Microcephaly