title: Genotype and phenotype in 12 additional individuals with SATB2-associated syndrome.
abstract: SATB2-associated syndrome (SAS) is a multisystemic disorder caused by alterations of the SATB2 gene. We describe the phenotype and genotype of 12 individuals with 10 unique (de novo in 11 of 11 tested) pathogenic variants (1 splice site, 5 frameshift, 3 nonsense, and 2 missense) in SATB2 and review all cases reported in the published literature caused by point alterations thus far. In the cohort here described, developmental delay (DD) with severe speech compromise, facial dysmorphism, and dental anomalies were present in all cases. We also present the third case of tibial bowing in an individual who, just as in the previous 2 individuals in the literature, also had a truncating pathogenic variant of SATB2. We explore early genotype-phenotype correlations and reaffirm the main clinical features of this recognizable syndrome: universal DD with severe speech impediment, mild facial dysmorphism, and high frequency of craniofacial anomalies, behavioral issues, and brain neuroradiographic changes. As the recently proposed surveillance guidelines for individuals with SAS are adopted by providers, further delineation of the frequency and impact of other phenotypic traits will become available. Similarly, as new cases of SAS are identified, further exploration of genotype-phenotype correlations will be possible.
authors.affiliation: Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Y A
authors.identifier: http://orcid.org/0000-0001-8235-6200
authors.initials: YA
authors.lastname: Zarate
authors.affiliation: Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut.
authors.forename: L
authors.initials: L
authors.lastname: Kalsner
authors.affiliation: Department of Pediatrics, Cook Children's Physician Network, Fort Worth, Texas.
authors.forename: A
authors.initials: A
authors.lastname: Basinger
authors.affiliation: Department of Genetics, Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: J R
authors.initials: JR
authors.lastname: Jones
authors.affiliation: Clinical Genetics program, McMaster University Medical Center, Hamilton, Ontario, Canada.
authors.forename: C
authors.identifier: http://orcid.org/0000-0002-4207-6914
authors.initials: C
authors.lastname: Li
authors.affiliation: Clinical Genetics program, McMaster University Medical Center, Hamilton, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Szybowska
authors.affiliation: Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Xu
authors.affiliation: Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia.
authors.forename: S
authors.initials: S
authors.lastname: Vergano
authors.affiliation: Health Outcomes, Collage of pharmacy, University of Rhode Island, Kingston, Rhode Island.
authors.forename: A R
authors.initials: AR
authors.lastname: Caffrey
authors.affiliation: Biostatistics Program, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: C V
authors.initials: CV
authors.lastname: Gonzalez
authors.affiliation: Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: H
authors.initials: H
authors.lastname: Dubbs
authors.affiliation: Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: E
authors.initials: E
authors.lastname: Zackai
authors.affiliation: Department of Molecular Genetics, GeneDx, Gaithersburg, Maryland.
authors.forename: F
authors.initials: F
authors.lastname: Millan
authors.affiliation: Department of Molecular Genetics, GeneDx, Gaithersburg, Maryland.
authors.forename: A
authors.initials: A
authors.lastname: Telegrafi
authors.affiliation: Department of Molecular Genetics, GeneDx, Gaithersburg, Maryland.
authors.forename: B
authors.initials: B
authors.lastname: Baskin
authors.affiliation: Department of Molecular Genetics, GeneDx, Gaithersburg, Maryland.
authors.forename: R
authors.initials: R
authors.lastname: Person
authors.affiliation: Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts.
authors.forename: J L
authors.initials: JL
authors.lastname: Fish
authors.affiliation: Department of Genetics, Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: D B
authors.initials: DB
authors.lastname: Everman
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000503:physiopathology; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors
keywords: SATB2; cleft palate; tibial bowing; whole-exome sequencing