title: Coffin-Siris and Nicolaides-Baraitser syndromes are a common well recognizable cause of intellectual disability.
abstract: BACKGROUND
  Nicolaides-Baraitser and Coffin-Siris syndromes are emerging conditions with overlapping clinical features including intellectual disability and typical somatic characteristics, especially sparse hair, low frontal hairline, large mouth with thick and everted lips, and hands and feet anomalies. Since 2012, mutations in genes encoding six proteins of the BAF complex were identified in both conditions.
  
  
  RESULTS
  We have clinically evaluated a cohort of 1161 patients with intellectual disability from three different Italian centers. A strong clinical suspicion of either Nicolaides-Baraitser syndrome or Coffin-Siris syndrome was proposed in 11 cases who were then molecularly confirmed: 8 having de novo missense mutations in SMARCA2, two frame-shift mutations in ARID1B and one missense mutation in SMARCB1. Given the high frequency of the condition we set up a one-step deep sequencing test for all 6 genes of the BAF complex.
  
  
  CONCLUSIONS
  These results prove that the frequency of these conditions may be as high as the most common syndromes with intellectual deficit (about 1%). Clinical geneticists should be well aware of this group of disorders in the clinical setting when ascertaining patients with intellectual deficit, the specific facial features being the major diagnostic handle. Finally, this work adds information on the clinical differences of the two conditions and presents a fast and sensitive test for the molecular diagnosis.
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy. Electronic address: francesca.mari@unisi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.affiliation: Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Annabella
authors.initials: A
authors.lastname: Marozza
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Mencarelli
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Lo Rizzo
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fallerini
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Dosa
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Marco
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Carignani
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Baldassarri
authors.affiliation: Pediatric Department at Monza Brianza per il Bambino e la sua Mamma (MBBM) Foundation, Pediatric Genetic Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cianci
authors.affiliation: Pediatric Unit, University of Siena, Siena, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Vivarelli
authors.affiliation: Pediatric Unit, University of Siena, Siena, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Vascotto
authors.affiliation: Pediatric Unit, University of Siena, Siena, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grosso
authors.affiliation: Dept of Clinical Medicine and Immunological Science, Dermatology Section, University of Siena, Siena, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Rubegni
authors.affiliation: Dept of Internal Medicine, Endocrine-Metabolic Science and Biochemistry, University of Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Caffarelli
authors.affiliation: Medical, Surgical and Neurological Sciences, Neurodegenerative Disease Unit, University of Siena, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pretegiani
authors.affiliation: Dept of Clinical Medicine and Immunological Science, Dermatology Section, University of Siena, Siena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Fimiani
authors.affiliation: Clinical Genetics Unit, Obstetric and Paediatric Department, Istituto di Ricovero e Cura a Carattere Scientifico, Arcispedale S Maria Nuova, Reggio Emilia, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.affiliation: Center for Human Genetics, KU Leuven, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cristofoli
authors.affiliation: Center for Human Genetics, KU Leuven, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.affiliation: Dept of Internal Medicine, Endocrine-Metabolic Science and Biochemistry, University of Siena, Italy.
authors.forename: Ranuccio
authors.initials: R
authors.lastname: Nuti
authors.affiliation: Medical, Surgical and Neurological Sciences, Neurodegenerative Disease Unit, University of Siena, Siena, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.affiliation: Pediatric Unit, University of Siena, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Balestri
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, AOUS, Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
authors.affiliation: Pediatric Department at Monza Brianza per il Bambino e la sua Mamma (MBBM) Foundation, Pediatric Genetic Unit, San Gerardo Hospital, Monza, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Selicorni
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D005532:Foot Deformities, Congenital / Q000150:complications / Q000235:genetics; D056726:Genetic Association Studies; D006228:Hand Deformities, Congenital / Q000150:complications / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007039:Hypotrichosis / Q000150:complications / Q000235:genetics; D007223:Infant; D008607:Intellectual Disability / Q000150:complications / Q000209:etiology* / Q000235:genetics; D008297:Male; D008844:Micrognathism / Q000150:complications / Q000235:genetics*; D009333:Neck / Q000002:abnormalities*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics
chemical_list: C497837:ARID1B protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors
keywords: ARID1B; BAF-complex; Coffin–Siris syndrome; Nicolaides–Baraitser syndrome; SMARCA2; SMARCB1