Biallelic inactivating variants in the GTPBP2 gene cause a neurodevelopmental disorder with severe intellectual disability

Aida M. Bertoli-Avella, Jose M. Garcia-Aznar, Oliver Brandau, Fahad Al-Hakami, Zafer Yüksel, Anett Marais, Nana Maria Grüning, Lia Abbasi Moheb, Omid Paknia, Nahla Alshaikh, Seham Alameer, Makia J. Marafi, Fahd Al-Mulla, Nouriya Al-Sannaa, Arndt Rolfs, Peter Bauer

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Congenital neurological disorders are genetically highly heterogeneous. Rare forms of hereditary neurological disorders are still difficult to be adequately diagnosed. Pertinent studies, especially when reporting only single families, need independent confirmation. We present three unrelated families in which whole-exome sequencing identified the homozygous non-sense variants c.430[C>T];[C>T] p.(Arg144∗), c.1219[C>T];[C>T] p.(Gln407∗) and c.1408[C>T];[C>T] p.(Arg470∗) in GTPBP2. Their clinical presentations include early onset and apparently non-progressive motor and cognitive impairment, and thereby overlap with findings in a recently described family harbouring a homozygous GTPBP2 splice site variant. Notable differences include structural brain abnormalities (e.g., agenesis of the corpus callosum, exclusive to our patients), and evidence for brain iron accumulation (exclusive to the previously described family). This report confirms pathogenicity of biallelic GTPBP2 inactivation and broadens the phenotypic spectrum. It also underlines that a potential involvement of brain iron accumulation needs clarification. Further patients will have to be identified and characterised in order to fully define the core features of GTPBP2-associated neurological disorder, but future approaches to molecular diagnosis of neurodevelopmental disorders should implement GTPBP2.

Original languageEnglish
Pages (from-to)592-598
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number4
Publication statusPublished - 1 Apr 2018


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