Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00843989%3A_____%2F23%3AE0110410" target="_blank" >RIV/00843989:_____/23:E0110410 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/23:10478505 RIV/00064165:_____/23:10478505
Result on the web
<a href="https://academic.oup.com/hmg/article-abstract/32/18/2822/7210301?redirectedFrom=fulltext&login=true" target="_blank" >https://academic.oup.com/hmg/article-abstract/32/18/2822/7210301?redirectedFrom=fulltext&login=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/hmg/ddad109" target="_blank" >10.1093/hmg/ddad109</a>
Alternative languages
Result language
angličtina
Original language name
Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome
Original language description
Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogeneous disorders characterized by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in over 20 genes encoding ciliary proteins have been found to cause OFDS through deleterious structural or functional impacts on primary cilia. We identified by exome sequencing bi-allelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families. Affected individuals presented a novel form of OFDS (OFDS-RAB34) accompanied by cardiac, cerebral, skeletal and anorectal defects. RAB34 encodes a member of the Rab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Unlike many genes required for cilium assembly, RAB34 acts selectively in cell types that use the intracellular ciliogenesis pathway, in which nascent cilia begin to form in the cytoplasm. We find that the protein products of these pathogenic variants, which are clustered near the RAB34 C-terminus, exhibit a strong loss of function. Although some variants retain the ability to be recruited to the mother centriole, cells expressing mutant RAB34 exhibit a significant defect in cilium assembly. While many Rab proteins have been previously linked to ciliogenesis, our studies establish RAB34 as the first small GTPase involved in OFDS and reveal the distinct clinical manifestations caused by impairment of intracellular ciliogenesis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human molecular genetics
ISSN
0964-6906
e-ISSN
1460-2083
Volume of the periodical
32
Issue of the periodical within the volume
18
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
2822-2831
UT code for WoS article
001167730000003
EID of the result in the Scopus database
2-s2.0-85168683501