E-resources
Peer reviewed
Open access
-
Salpietro, Vincenzo; Maroofian, Reza; Wangen, Jamie; Ciolfi, Andrea; Barresi, Sabina; Efthymiou, Stephanie; Aughey, Gabriel N.; Al Mutairi, Fuad; Accogli, Andrea; Zara, Federico; Tariq, Huma; Rehman, Khalil Ur; Abd Elmaksoud, Marwa; El Said, Huda G.; Al Shalan, Maha; Khang, Rin; Elbendary, Hasnaa M.; Marinakis, Nikolaos M.; Traeger-Synodinos, Joanne; Ververi, Athina; Sourmpi, Mara; Khadivi Zand, Farhad; Beiraghi Toosi, Mehran; Hannah, Michael G.; Bertini, Enrico; Aguennouz, Mhammed; Groppa, Stanislav; Kathom, Hadil; Tincheva, Radka; Verrotti, Alberto; Macaya, Alfons; Garavaglia, Barbara; Cortese, Andrea; Sullivan, Roisin; Papanicolaou, Eleni Z.; Dardiotis, Efthymios; Maqbool, Shazia; Ibrahim, Shahnaz; Rana, Nuzhat N.; Atawneh, Osama; Zuccotti, Gian V.; Marseglia, Gian L.; Shaikh, Farooq; Corsello, Giovanni; Mangano, Salvatore; Koutsis, George; Scuderi, Carmela; Ferrara, Pietro; Zollo, Massimo; Berni-Canani, Roberto; Sisto, Antonio; Strano, Federica; Di Francesco, Ludovica; Salayev, Kamran; Xiromerisiou, Georgia; Munell, Francina; Gagliano, Antonella; Jan, Farida; Chimenz, Roberto; Di Rosa, Gabriella; Pettoello-Mantovani, Massimo; Tazir, Meriem; Farello, Giovanni; Delvecchio, Maurizio; Di-Donato, Giulio; Obeid, Makram; Saadi, Nebal W.; Maccarone, Rita; Kara, Majdi; Karimiani, Ehsan G.; Seri, Marco; Di-Falco, Giovanna; Barrano, Giuseppe; Operto, Francesca F.; Valenzise, Mariella; Matricardi, Sara; Zafar, Faisal; Ullah, Ehsan; Afzal, Erum; Rahman, Fatima; De Filippo, Maria; Licari, Amelia; Trebbi, Edoardo; Romano, Ferdinando; Heimer, Gali; Al-Khawaja, Issam; Al-Mutairi, Fuad; Shashkin, Chingiz; Koneyev, Kairgali; Pagnamenta, Alistair T.; Corsello, Antonio; Dallapiccola, Bruno; Alobeid, Eman; Mankad, Kshitij; Ghayoor-Karimiani, Ehsan; Chung, Wendy K.; Green, Rachel; Alkuraya, Fowzan S.; Jepson, James E.C.; Houlden, Henry
American journal of human genetics, 01/2024, Volume: 111, Issue: 1Journal Article
The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species. Display omitted Bi-allelic variants in the translational GTPases GTPBP1 and GTPBP2 may affect ribosomal translational control and impair brain development and neurological function. This research identifies 20 individuals with homozygous GTPBP1 and GTPBP2 variants leading to an identical neurodevelopmental syndrome, which we defined as “Gtpbp1/2-related ectodermal neurodevelopmental (GREND) syndrome.”
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.