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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2016

Open Access 01-12-2016 | Research article

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

Authors: André Mégarbané, Rashid Al-Ali, Nancy Choucair, Monko Lek, Ena Wang, Moncef Ladjimi, Catherine M. Rose, Remy Hobeika, Yvette Macary, Ramzi Temanni, Puthen V. Jithesh, Aouatef Chouchane, Konduru S Sastry, Remy Thomas, Sara Tomei, Wei Liu, Francesco M. Marincola, Daniel MacArthur, Lotfi Chouchane

Published in: BMC Medical Genetics | Issue 1/2016

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Abstract

Background

KCNH1 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).

Methods

Here, 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.

Results

Whole 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.

Conclusions

Our 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.
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Metadata
Title
Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome: one clinical entity?
Authors
André Mégarbané
Rashid Al-Ali
Nancy Choucair
Monko Lek
Ena Wang
Moncef Ladjimi
Catherine M. Rose
Remy Hobeika
Yvette Macary
Ramzi Temanni
Puthen V. Jithesh
Aouatef Chouchane
Konduru S Sastry
Remy Thomas
Sara Tomei
Wei Liu
Francesco M. Marincola
Daniel MacArthur
Lotfi Chouchane
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2016
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-016-0304-4

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