AMELX mutations and genotype-phenotype correlation in x-linked amelogenesis imperfecta

Basit Öğe Kaydı
dc.contributor.authorWang, Shih-Kai
dc.contributor.authorZhang, Hong
dc.contributor.authorLin, Hua-Chieh
dc.contributor.authorWang, Yin-Lin
dc.contributor.authorLin, Shu-Chun
dc.contributor.authorSeymen, Figen
dc.contributor.authorKoruyucu, Mine
dc.contributor.authorSimmer, James P.
dc.contributor.authorHu, Jan C.-C.
dc.date.accessioned2024-07-09T08:36:02Z
dc.date.available2024-07-09T08:36:02Z
dc.date.issued2024en_US
dc.departmentFakülteler, Diş Hekimliği Fakültesi, Çocuk Diş Hekimliği Ana Bilim Dalıen_US
dc.description.abstractAMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype-phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5' truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3' truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins.en_US
dc.identifier.citationWang, S.-K., Zhang, H., Lin, H.-C., Wang, Y.-L., Lin, S.-C., Seymen, F., Koruyucu, M., Simmer, J. P., Hu, J. C.-C. (2024). AMELX mutations and genotype-phenotype correlation in x-linked amelogenesis imperfecta. International Journal of Molecular Sciences, 25(11). 10.3390/ijms25116132en_US
dc.identifier.issn1422-0067
dc.identifier.issue11en_US
dc.identifier.scopus2-s2.0-85195834132
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://hdl.handle.net/20.500.12939/4735
dc.identifier.volume25en_US
dc.identifier.wosWOS:001246886100001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorSeymen, Figen
dc.language.isoen
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.isversionof10.3390/ijms25116132en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectER stressen_US
dc.subjectAmeloblasten_US
dc.subjectAmelogeninen_US
dc.subjectApoptosisen_US
dc.subjectBiomineralizationen_US
dc.subjectDental enamelen_US
dc.subjectIyonizationen_US
dc.subjectProtein secretionen_US
dc.subjectSignal peptideen_US
dc.subjectUnfolded protein responseen_US
dc.titleAMELX mutations and genotype-phenotype correlation in x-linked amelogenesis imperfecta
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
ijms-25-06132.pdf
Boyut:
15.9 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
[ X ]
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

PubMed İndeksli Yayınlar Koleksiyonu
Diş Hekimliği Fakültesi Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu