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Cited by 4dental development and anomaliesBone and Dental Protein StudiesHair Growth and Disorders

Novel LRP6 Mutations Causing Non-Syndromic Oligodontia

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Lee, Yejin, Chae, Wonseon, Kim, Youn Jung, Kim, Jung-Wook·2022·Journal of Personalized Medicine
DOI 10.3390/jpm12091401PMC PMC9504909
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Abstract

The process of tooth formation is a series of reciprocal interactions between the ectoderm and mesoderm, and it is believed that many genetic factors are involved in this complex process. More than a dozen genes have been identified in non-syndromic tooth agenesis; however, the genetic etiology underlying tooth agenesis is not fully understood yet. In this study, we identified two novel LRP6 mutations in two non-syndromic oligodontia families. Both probands had 16 and 17 missing teeth in their permanent dentition. Mutational analysis identified a de novo frameshift mutation by a 1-bp insertion in exon 9 (NM_002336.2: c.1870dupA, p.(Met624Asnfs*29)) and a splicing donor site mutation in intron 8 (c.1762+2T>C). An in vitro splicing assay confirmed the deletion of exon 8, and the deletion would result in a frameshift. Due to the premature termination codons introduced by the frameshift, both mutant transcripts would be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency.

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  • The effect of this presumably dominant-negative mutation on early development may be more widespread than that of previously described pathogenic LRP6 variants.

    “Therefore, the effect of this presumably dominant-negative mutation on early development may be more widespread than that of previously described pathogenic LRP6 variants [54,55].”

    From Molecular Pathway-Based Classification of Ectodermal Dysplasias: First Five-Yearly Update (2022) · cites this paper as [55]

    The Discussion describes a previously reported LRP6 frameshift associated with orofacial clefting and suggests its dominant-negative effect would be more harmful than that of other frameshift mutations degraded by nonsense-mediated decay. It does not compare the citing paper’s mutation with previously described LRP6 variants or establish that its effects on early development may be more widespread. The Conclusions describe this paper’s two newly identified mutations as predicted to cause transcript degradation, not dominant-negative effects. (LLM, conf=0.84)

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References 47 · Cited by 4

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Authors
Lee, Y., Chae, W., Kim, Y. J., & Kim, J.-W.
Affiliations
Seoul National University (KR)
Corresponding author
Kim, Jung-Wook
ORCID
Venue
Journal of Personalized Medicine
Publisher
MDPI AG
Published
2022-08-29
Volume
12
Issue
9
Pages
1401
ISSN
2075-4426 (ISSN-L)
DOI
10.3390/jpm12091401
PMC
PMC9504909
OpenAlex
W4293724057
Cited by
4
References
47
Citations by year
2026: 2 · 2024: 1 · 2022: 1
FWCI
0.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Personalized Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
Funders
National Research Foundation of Korea (NRF) (NRF-2018R1A5A2024418, NRF-2020R1A2C2100543)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
  • Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
Keywords
LRP6, non-syndromic oligodontia, tooth agenesis, novel mutations, frameshift mutation, nonsense-mediated mRNA decay, haploinsufficiency, tooth development, genetic etiology

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