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A novel mutation in CDH11 , encoding cadherin‐11, cause Branchioskeletogenital (Elsahy‐Waters) syndrome
Author(s) -
Castori Marco,
Ott ClausEric,
Bisceglia Luigi,
Leone Maria Pia,
Mazza Tommaso,
Castellana Stefano,
Tomassi Jurgen,
Lanciotti Silvia,
Mundlos Stefan,
Hennekam Raoul C.,
Kornak Uwe,
Brancati Francesco
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.40379
Subject(s) - cadherin , biology , craniofacial , genetics , morphogenesis , exon , mutation , nonsense mutation , mendelian inheritance , zebrafish , exome sequencing , microbiology and biotechnology , gene , cell , missense mutation
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.