Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome: one clinical entity?

BMC Medical Genetics

Research Article

Ramzi Temanni¹  Puthen V. Jithesh¹  Rashid Al-Ali¹  Konduru S Sastry²  Aouatef Chouchane²  Ena Wang³  Wei Liu³  Sara Tomei³  André Mégarbané⁴  Nancy Choucair⁴  Yvette Macary⁴  Remy Hobeika⁴  Remy Thomas⁵  Lotfi Chouchane⁵  Moncef Ladjimi⁶  Monko Lek⁷  Daniel MacArthur⁷  Catherine M. Rose⁸  Francesco M. Marincola⁹ 

[1] Bioinformatics Division, Sidra Medical & Research Center, Doha, Qatar;Dermatology Research Group, Translational Medicine Division, Sidra Medical & Research Center, Doha, Qatar;Genomics Core Laboratory, Translational Medicine Division, Sidra Medical & Research Center, Doha, Qatar;Institut Jérôme Lejeune, Paris, France;Laboratory of Genetic Medicine and Immunology, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar;Laboratory of Protein Chemistry, Weill Cornell Medicine-Qatar, Doha, Qatar;Medical and Population Genetics, Broad Institute of Harvard Medical School, Boston, USA;POSSUMweb, Victorian Clinical Genetics Service and Murdoch Childrens Research Institute, The Royal Children’s Hospital, Parkville, VIC, Australia;Research Office, Sidra Medical & Research Center, Doha, Qatar;

关键词: Temple-Baraitser syndrome;    Whole genome sequencing;    KCNH1;    Zimmermann-Laband syndrome;   

DOI  :  10.1186/s12881-016-0304-4

 received in 2016-04-15, accepted in 2016-06-02,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundKCNH1 encodes a voltage-gated potassium channel that is predominantly expressed in the central nervous system. Mutations in this gene were recently found to be responsible for Temple-Baraitser Syndrome (TMBTS) and Zimmermann-Laband syndrome (ZLS).MethodsHere, we report a new case of TMBTS diagnosed in a Lebanese child. Whole genome sequencing was carried out on DNA samples of the proband and his parents to identify mutations associated with this disease. Sanger sequencing was performed to confirm the presence of detected variants.ResultsWhole genome sequencing revealed three missense mutations in TMBTS patient: c.1042G > A in KCNH1, c.2131 T > C in STK36, and c.726C > A in ZNF517. According to all predictors, mutation in KCNH1 is damaging de novo mutation that results in substitution of Glycine by Arginine, i.e., p.(Gly348Arg). This mutation was already reported in a patient with ZLS that could affect the connecting loop between helices S4-S5 of KCNH1 with a gain of function effect.ConclusionsOur findings demonstrate that KCNH1 mutations cause TMBTS and expand the mutational spectrum of KCNH1 in TMBTS. In addition, all cases of TMBTS were reviewed and compared to ZLS. We suggest that the two syndromes are a continuum and that the variability in the phenotypes is the result of the involvement of genetic modifiers.

【 授权许可】

CC BY   
© The Author(s). 2016