title: Further delineation of the SATB2 phenotype.
abstract: SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial role in craniofacial patterning and osteoblast differentiation, as well as in determining the fates of neuronal projections in the developing neocortex. In humans, chromosomal translocations and deletions of 2q33.1 leading to SATB2 haploinsufficiency are associated with cleft palate (CP), facial dysmorphism and intellectual disability (ID). A single patient carrying a nonsense mutation in SATB2 has been described to date. In this study, we performed trio-exome sequencing in a 3-year-old girl with CP and severely delayed speech development, and her unaffected parents. Previously, the girl had undergone conventional and molecular karyotyping (microarray analysis), as well as targeted analysis for different diseases associated with developmental delay, including Angelman syndrome, Rett syndrome and Fragile X syndrome. No diagnosis could be established. Exome sequencing revealed a de novo nonsense mutation in the SATB2 gene (c.715C>T; p.R239*). The identification of a second patient carrying a de novo nonsense mutation in SATB2 confirms that this gene is essential for normal craniofacial patterning and cognitive development. Based on our data and the literature published so far, we propose a new clinically recognizable syndrome - the SATB2-associated syndrome (SAS). SAS is likely to be underdiagnosed and should be considered in children with ID, severe speech delay, cleft or high-arched palate and abnormal dentition with crowded and irregularly shaped teeth.
authors.affiliation: Institute of Clinical Genetics, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Döcker
authors.affiliation: CeGaT GmbH, Tübingen, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Schubach
authors.affiliation: CeGaT GmbH, Tübingen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Menzel
authors.affiliation: Hertie Institute for Clinical Brain Research, Tübingen, Germany.
authors.forename: Marita
authors.initials: M
authors.lastname: Munz
authors.affiliation: Institute of Clinical Genetics, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Spaich
authors.affiliation: 1] Institute of Clinical Genetics, Klinikum Stuttgart, Stuttgart, Germany [2] CeGaT GmbH, Tübingen, Germany [3] Hertie Institute for Clinical Brain Research, Tübingen, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Biskup
authors.affiliation: Institute of Clinical Genetics, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bartholdi
mesh_terms: D002675:Child, Preschool; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D059472:Exome; D019066:Facies; D005260:Female; D023061:Gene Order; D056726:Genetic Association Studies; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors