TY - JOUR
T1 - A novel mutation in CDH11, encoding cadherin-11, cause Branchioskeletogenital (Elsahy-Waters) syndrome
AU - Castori, Marco
AU - Ott, Claus-Eric
AU - Bisceglia, Luigi
AU - Leone, Maria Pia
AU - Mazza, Tommaso
AU - Castellana, Stefano
AU - Tomassi, Jurgen
AU - Lanciotti, Silvia
AU - Mundlos, Stefan
AU - Hennekam, Raoul C.
AU - Kornak, Uwe
AU - Brancati, Francesco
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052957534&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30194892
U2 - https://doi.org/10.1002/ajmg.a.40379
DO - https://doi.org/10.1002/ajmg.a.40379
M3 - Article
C2 - 30194892
SN - 1552-4825
VL - 176
SP - 2028
EP - 2033
JO - American journal of medical genetics. Part A
JF - American journal of medical genetics. Part A
IS - 9
ER -