Pathogenic variants in CDH11 impair cell adhesion and cause Teebi hypertelorism syndrome
Dong Li, Michael E March, Paola Fortugno, Liza L Cox, Leticia S Matsuoka, Rosanna Monetta, Christoph Seiler, Louise C Pyle, Emma C Bedoukian, Maria Jose Sanchez-Soler, Oana Caluseriu, Katheryn Grand, Allison Tam, Alicia RP Aycinena, Letizia Camerota, Yiran Guo, Patrick Sleiman, Bert Callewaert, Candy Kumps, Annelies Dheedene Show all
HUMAN GENETICS | SPRINGER | Published : 2021
Teebi hypertelorism syndrome (THS; OMIM 145420) is a rare craniofacial disorder characterized by hypertelorism, prominent forehead, short nose with broad or depressed nasal root. Some cases of THS have been attributed to SPECC1L variants. Homozygous variants in CDH11 truncating the transmembrane and intracellular domains have been implicated in Elsahy-Waters syndrome (EWS; OMIM 211380) with hypertelorism. We report THS due to CDH11 heterozygous missense variants on 19 subjects from 9 families. All affected residues in the extracellular region of Cadherin-11 (CHD11) are highly conserved across vertebrate species and classical cadherins. Six of the variants that cluster around the EC2-EC3 and ..View full abstract
Research reported in this publication was supported in part by the Roberts Collaborative Functional Genomics Rapid Grant (to D.L., C.S., L.P.) from CHOP. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. F.B. acknowledges for support and is member of the Italian Undiagnosed Rare Diseases Network led by Dr. Domenica Taruscio (Director, National Centre for Rare Diseases, Istituto Superiore Sanita, Italy). We would like to thank Prof. Ian Glass and Mei Deng, Birth Defects Research Laboratory, University of Washington, for conceptual tissues.