title: A mutation in COL4A2 causes autosomal dominant porencephaly with cataracts.
abstract: Mutations in COL4A1 are well described and result in brain abnormalities manifesting with severe neurological deficits including cerebral palsy, intellectual disability, and focal epilepsy. Families with mutations in COL4A2 are now emerging with a similar phenotype. We describe a family with an autosomal dominant disorder comprising porencephaly, focal epilepsy, and lens opacities, which was negative for mutations in COL4A1. Using whole exome sequencing of three affected individuals from three generations, we identified a rare variant in COL4A2. This COL4A2 (c.2399G>A, p.G800E, CCDS41907.1) variant was predicted to be damaging by multiple bioinformatics tools and affects an invariable glycine residue that is essential for the formation of collagen IV heterotrimers. The cataracts identified in this family expand the phenotypic spectrum associated with mutations in COL4A2 and highlight the increasing overlap with phenotypes associated with COL4A1 mutations.
authors.affiliation: School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Thuong T
authors.initials: TT
authors.lastname: Ha
authors.affiliation: Department of Paediatrics and Child Health, University of Otago Wellington, Wellington South, New Zealand.
authors.forename: Lynette G
authors.initials: LG
authors.lastname: Sadleir
authors.affiliation: Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia.|Department of Radiology, University of Melbourne, Royal Children's Hospital Parkville, Melbourne, Victoria, Australia.|Florey Institute of Neurosciences and Mental Health, Heidelberg, Victoria, Australia.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Mandelstam
authors.affiliation: Department of Paediatrics and Child Health, University of Otago Wellington, Wellington South, New Zealand.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Paterson
authors.affiliation: Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia.|Florey Institute of Neurosciences and Mental Health, Heidelberg, Victoria, Australia.|Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia.|Department of Medicine, Austin Health, University of Melbourne, Victoria, Australia.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.affiliation: School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.|Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.|Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Corbett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D002386:Cataract / Q000175:diagnosis* / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D059472:Exome; D005260:Female; D005799:Genes, Dominant; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010375:Pedigree; D065708:Porencephaly / Q000175:diagnosis* / Q000235:genetics*
chemical_list: C502625:COL4A2 protein, human; D024141:Collagen Type IV
keywords: COL4A1; COL4A2; autosomal dominant; cataracts; epilepsy; porencephaly