The modified shields classification and 12 families with defined dspp mutations
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Dosyalar
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentino-genesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5′-DSPP mutations, and 3′-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5′-Dspp or 3′-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-DSPP defects be diagnosed as DGI-III, while those with 3′-DSPP defects be diagnosed as DGI-II.
Açıklama
Anahtar Kelimeler
Dentin Dyspla-Sia, Dentinogenesis Imperfecta, DSPP Mutations, Enamel Malformations, Shields Classification, Single Molecule Real-Time (SMRT) DNA Sequencing, Whole-Exome Sequencing (WES)
Kaynak
Genes
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
13
Sayı
5
Künye
Simmer, J. P., Zhang, H., Moon, S. J., Donnelly, L. A., Lee, Y. L., Seymen, F., ... & Hu, J. C. C. (2022). The modified shields classification and 12 families with defined DSPP mutations. Genes, 13(5), 858.
