Francesca Mari1, Annabella Marozza2, Maria Antonietta Mencarelli3, Caterina Lo Rizzo3, Chiara Fallerini4, Laura Dosa3, Chiara Di Marco3, Giulia Carignani3, Margherita Baldassarri3, Paola Cianci5, Rossella Vivarelli6, Marina Vascotto6, Salvatore Grosso6, Pietro Rubegni7, Carla Caffarelli8, Elena Pretegiani9, Michele Fimiani7, Livia Garavelli10, Francesca Cristofoli11, Joris R Vermeesch11, Ranuccio Nuti8, Maria Teresa Dotti9, Paolo Balestri6, Joussef Hayek12, Angelo Selicorni5, Alessandra Renieri3. 1. Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy. Electronic address: francesca.mari@unisi.it. 2. Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy. 3. Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy. 4. Medical Genetics, University of Siena, Siena, Italy. 5. Pediatric Department at Monza Brianza per il Bambino e la sua Mamma (MBBM) Foundation, Pediatric Genetic Unit, San Gerardo Hospital, Monza, Italy. 6. Pediatric Unit, University of Siena, Siena, Italy. 7. Dept of Clinical Medicine and Immunological Science, Dermatology Section, University of Siena, Siena, Italy. 8. Dept of Internal Medicine, Endocrine-Metabolic Science and Biochemistry, University of Siena, Italy. 9. Medical, Surgical and Neurological Sciences, Neurodegenerative Disease Unit, University of Siena, Siena, Italy. 10. Clinical Genetics Unit, Obstetric and Paediatric Department, Istituto di Ricovero e Cura a Carattere Scientifico, Arcispedale S Maria Nuova, Reggio Emilia, Italy. 11. Center for Human Genetics, KU Leuven, University Hospital Gasthuisberg, Leuven, Belgium. 12. Child Neuropsychiatry Unit, University Hospital, AOUS, Siena, Italy.
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. METHODS AND 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.
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. METHODS AND 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: Salma Ben-Salem; Nara Sobreira; Nadia A Akawi; Aisha M Al-Shamsi; Anne John; Thachillath Pramathan; David Valle; Bassam R Ali; Lihadh Al-Gazali Journal: Am J Med Genet A Date: 2015-09-23 Impact factor: 2.802
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Authors: Ronit Marom; Mahim Jain; Lindsay C Burrage; I-Wen Song; Brett H Graham; Chester W Brown; Servi J C Stevens; Alexander P A Stegmann; Andrew T Gunter; Julie D Kaplan; Ralitza H Gavrilova; Marwan Shinawi; Jill A Rosenfeld; Yangjin Bae; Alyssa A Tran; Yuqing Chen; James T Lu; Richard A Gibbs; Christine Eng; Yaping Yang; Justine Rousseau; Bert B A de Vries; Philippe M Campeau; Brendan Lee Journal: Hum Mutat Date: 2017-07-10 Impact factor: 4.878
Authors: Benjamin W Darbro; Rohini Singh; M Bridget Zimmerman; Vinit B Mahajan; Alexander G Bassuk Journal: PLoS One Date: 2016-03-02 Impact factor: 3.240