title: Mutations in TNK2 in severe autosomal recessive infantile onset epilepsy.
abstract: We identified a small family with autosomal recessive, infantile onset epilepsy and intellectual disability. Exome sequencing identified a homozygous missense variant in the gene TNK2, encoding a brain-expressed tyrosine kinase. Sequencing of the coding region of TNK2 in 110 patients with a similar phenotype failed to detect further homozygote or compound heterozygote mutations. Pathogenicity of the variant is supported by the results of our functional studies, which demonstrated that the variant abolishes NEDD4 binding to TNK2, preventing its degradation after epidermal growth factor stimulation. Definitive proof of pathogenicity will require confirmation in unrelated patients.
authors.affiliation: Duke Center for Human Genome Variation, Duke University School of Medicine, Durham, NC.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hitomi
authors.forename: Erin L
authors.initials: EL
authors.lastname: Heinzen
authors.forename: Simona
authors.initials: S
authors.lastname: Donatello
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Dahl
authors.forename: John A
authors.initials: JA
authors.lastname: Damiano
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: McMahon
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Legros
authors.forename: Myriam
authors.initials: M
authors.lastname: Rai
authors.forename: Sarah
authors.initials: S
authors.lastname: Weckhuysen
authors.forename: Arvid
authors.initials: A
authors.lastname: Suls
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Bogaert
authors.forename: Chantal
authors.initials: C
authors.lastname: Depondt
mesh_terms: D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D011505:Protein-Tyrosine Kinases; C403262:TNK2 protein, human