title: Identification of a syndrome comprising microcephaly and intellectual disability but not white matter disease associated with a homozygous c.676C>T p.R226W DEAF1 mutation.
abstract: We evaluated a 13-year-old East Pakistani male affected with microcephaly, apparent intellectual disability, hypotonia, and brisk reflexes without spasticity. His parents were first cousins. The patient also had a brother who was similarly affected and died at 10 years due to an accident. Previous SNP array testing showed a 1.63 Mb duplication at 16p13.11 of uncertain significance along with regions of homozygosity. Exome sequencing identified a known pathogenic homozygous alteration in DEAF1, c.676C>T (p.R226W), in this patient. The alteration had been reported in two individuals from a consanguineous Saudi Arabian family. Both individuals had microcephaly, intellectual disability, hypotonia, feeding difficulties, and poor growth. The patient reported here did not have evidence of white matter disease, as had been reported with prior patients. We conclude that this DEAF1 gene alteration caused this patient's symptoms and that white matter disease should not be considered a obligate feature of this syndrome.
authors.affiliation: Ambry Genetics, 15 Argonaut, Aliso Viejo, California.
authors.forename: Christian
authors.initials: C
authors.lastname: Gund
authors.affiliation: Ambry Genetics, 15 Argonaut, Aliso Viejo, California.
authors.forename: Zöe
authors.initials: Z
authors.lastname: Powis
authors.affiliation: Ambry Genetics, 15 Argonaut, Aliso Viejo, California.
authors.forename: Wendy
authors.initials: W
authors.lastname: Alcaraz
authors.affiliation: Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: Sonal
authors.initials: S
authors.lastname: Desai
authors.affiliation: Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baranano
mesh_terms: D000293:Adolescent; D058674:Chromosome Duplication; D004268:DNA-Binding Proteins; D059472:Exome; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D056784:Leukoencephalopathies / Q000235:genetics / Q000473:pathology; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000503:physiopathology; D009123:Muscle Hypotonia / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
chemical_list: C116013:DEAF1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: DEAF1 protein; clinical diagnostic sequencing; consanguinity; exome; human; intellectual disability; microcephaly