Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome

One clinical entity?

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article number42
JournalBMC Medical Genetics
Volume17
Issue number1
DOIs
Publication statusPublished - 10 Jun 2016

Fingerprint

Mutation
Genome
Voltage-Gated Potassium Channels
Missense Mutation
Glycine
Arginine
Temple-Baraitser Syndrome
Zimmerman Laband syndrome
Central Nervous System
Parents
Phenotype
DNA
Genes

Keywords

  • KCNH1
  • Temple-Baraitser syndrome
  • Whole genome sequencing
  • Zimmermann-Laband syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome : One clinical entity? / Mégarbané, André; Al-Ali, Rashid J.; Choucair, Nancy; Lek, Monko; Wang, Ena; Ladjimi, Moncef; Rose, Catherine M.; Hobeika, Remy; Macary, Yvette; Temanni, Ramzi; Jithesh, Puthen V.; Ismail EP Chouchane, Aouatef; Konduru, Seetharama S.; Thomas, Remy; Tomei, Sara; Liu, Wei; Marincola, Francesco M.; MacArthur, Daniel; Chouchane, Lotfi.

In: BMC Medical Genetics, Vol. 17, No. 1, 42, 10.06.2016.

Research output: Contribution to journalArticle

Mégarbané, André ; Al-Ali, Rashid J. ; Choucair, Nancy ; Lek, Monko ; Wang, Ena ; Ladjimi, Moncef ; Rose, Catherine M. ; Hobeika, Remy ; Macary, Yvette ; Temanni, Ramzi ; Jithesh, Puthen V. ; Ismail EP Chouchane, Aouatef ; Konduru, Seetharama S. ; Thomas, Remy ; Tomei, Sara ; Liu, Wei ; Marincola, Francesco M. ; MacArthur, Daniel ; Chouchane, Lotfi. / Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome : One clinical entity?. In: BMC Medical Genetics. 2016 ; Vol. 17, No. 1.
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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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AU - Lek, Monko

AU - Wang, Ena

AU - Ladjimi, Moncef

AU - Rose, Catherine M.

AU - Hobeika, Remy

AU - Macary, Yvette

AU - Temanni, Ramzi

AU - Jithesh, Puthen V.

AU - Ismail EP Chouchane, Aouatef

AU - Konduru, Seetharama S.

AU - Thomas, Remy

AU - Tomei, Sara

AU - Liu, Wei

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AU - MacArthur, Daniel

AU - Chouchane, Lotfi

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