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Talvet, Jüri, Pealk.

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Jüri Talvet ja Albert Lázaro Tinaut], lk. Artikkel on eesti keeles ilmunud pealkirja ""Kalevipoeg" - suur Euroopa eepos" all. Olev Saveli Science.

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Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 TLK2 in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects.

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Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types missense and C-terminal truncating. This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype.

This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2.

Copyright © The Authors. Published by Elsevier Inc. All rights reserved.

  • Talvet, Jüri, Pealk.
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