PMID- 32408545
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2075-4418 (Print)
IS  - 2075-4418 (Electronic)
IS  - 2075-4418 (Linking)
VI  - 10
IP  - 5
DP  - 2020 May 12
TI  - Novel Splice Site Pathogenic Variant of EFTUD2 Is Associated with Mandibulofacial 
      Dysostosis with Microcephaly and Extracranial Symptoms in Korea.
LID - 10.3390/diagnostics10050296 [doi]
LID - 296
AB  - Elongation factor Tu guanosine-5'-triphosphate (GTP) binding domain containing 2 
      (EFTUD2) encodes a major component of the spliceosomal GTPase and, if mutated, 
      causes mandibulofacial dysostosis with microcephaly (MFDM; MIM#610536). Despite 
      the increasing number of potentially pathogenic variants reported in the 
      literature, most previous studies have relied solely on in silico prediction of 
      the pathogenic potential of EFTUD2 variants, which may result in 
      misclassification of the variant's pathogenicity. Given the importance of the 
      functional verification of EFTUD2 variants, we identified a novel splice donor 
      site variant, c.271+1G>A of EFTUD2, whose pathogenicity was clearly verified at 
      the RNA level using a minigene assay. A child with MFDM, mixed hearing loss, 
      microcephaly, and a congenital cardiac defect was identified with this variant, 
      which arose in a de novo fashion. The minigene assay showed erroneous integration 
      of the 118 bp IVS3 of EFTUD2 exclusively among the c.271+1G>A variant clone. We 
      first applied the minigene assay to identify the splice function of a splice site 
      variant of EFTUD2, thereby allowing for in vitro functional verification of 
      splice site variants in EFTUD2.
FAU - Kim, So Young
AU  - Kim SY
AUID- ORCID: 0000-0002-7361-4930
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical 
      Center, CHA University, Seongnam 13496, Korea.
FAU - Lee, Da-Hye
AU  - Lee DH
AUID- ORCID: 0000-0001-8909-2770
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical 
      Center, CHA University, Seongnam 13496, Korea.
FAU - Han, Jin Hee
AU  - Han JH
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National 
      University Bundang Hospital, Seongnam 13496, Korea.
FAU - Choi, Byung Yoon
AU  - Choi BY
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National 
      University Bundang Hospital, Seongnam 13496, Korea.
LA  - eng
GR  - 2018R1A2B2001054 to BYC/National Research Foundation of Korea/
GR  - HI17C0952/Korea Health Technology R&D Project/
GR  - 2018-0-00861/Institute of Information & communications Technology Planning & 
      evaluation(IITP) grant/
PT  - Journal Article
DEP - 20200512
PL  - Switzerland
TA  - Diagnostics (Basel)
JT  - Diagnostics (Basel, Switzerland)
JID - 101658402
PMC - PMC7277841
OTO - NOTNLM
OT  - EFTUD2
OT  - exome sequencing
OT  - mandibulofacial dysostosis
OT  - splicing
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/05/16 06:00
MHDA- 2020/05/16 06:01
PMCR- 2020/05/12
CRDT- 2020/05/16 06:00
PHST- 2020/03/23 00:00 [received]
PHST- 2020/04/28 00:00 [revised]
PHST- 2020/05/11 00:00 [accepted]
PHST- 2020/05/16 06:00 [entrez]
PHST- 2020/05/16 06:00 [pubmed]
PHST- 2020/05/16 06:01 [medline]
PHST- 2020/05/12 00:00 [pmc-release]
AID - diagnostics10050296 [pii]
AID - diagnostics-10-00296 [pii]
AID - 10.3390/diagnostics10050296 [doi]
PST - epublish
SO  - Diagnostics (Basel). 2020 May 12;10(5):296. doi: 10.3390/diagnostics10050296.