A novel mutation in CDH11, encoding cadherin‐11, cause Branchioskeletogenital (Elsahy‐Waters) syndrome |
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Authors: | Marco Castori Claus‐Eric Ott Luigi Bisceglia Maria Pia Leone Tommaso Mazza Stefano Castellana Jurgen Tomassi Silvia Lanciotti Stefan Mundlos Raoul C Hennekam Uwe Kornak Francesco Brancati |
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Institution: | 1. Division of Medical Genetics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy;2. Institute of Medical and Human Genetics, Charité ‐ Universit?tsmedizin Berlin, Berlin, Germany;3. Bioinformatics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy;4. Neurological Rehabilitation Unit, San Raffaele Hospital, Cassino, Italy;5. Medical Genetics Residency Programme, Tor Vergata University, Rome, Italy;6. Max Planck Institute for Molecular Genetics, Development and Disease Group, Berlin, Germany;7. Department of Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;8. Berlin‐Brandenburg Center for Regenerative Therapies, Charité ‐ Universit?tsmedizin Berlin, Germany;9. Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy;10. Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata (IDI) IRCCS, Rome, Italy |
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Abstract: | Cadherins are cell‐adhesion molecules that control morphogenesis, cell migration, and cell shape changes during multiple developmental processes. Until now four distinct cadherins have been implicated in human Mendelian disorders, mainly featuring skin, retinal and hearing manifestations. Branchio‐skeleto‐genital (or Elsahy‐Waters) syndrome (BSGS) is an ultra‐rare condition featuring a characteristic face, premature loss of teeth, vertebral and genital anomalies, and intellectual disability. We have studied two sibs with BSGS originally described by Castori et al. in 2010. Exome sequencing led to the identification of a novel homozygous nonsense variant in the first exon of the cadherin‐11 gene (CDH11), which results in a prematurely truncated form of the protein. Recessive variants in CDH11 have been recently demonstrated in two other sporadic patients and a pair of sisters affected by BSGS. Although the function of this cadherin (also termed Osteoblast‐Cadherin) is not completely understood, its prevalent expression in osteoblastic cell lines and up‐regulation during differentiation suggest a specific function in bone formation and development. This study identifies a novel loss‐of‐function variant in CDH11 as a cause of BSGS and supports the role of cadherin‐11 as a key player in axial and craniofacial malformations. |
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Keywords: | Branchioskeletogenital Elsahy‐Waters CDH11 Cadherin‐11 |
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