Phenotypic variability in LAMA3-associated amelogenesis imperfecta
[ X ]
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Objective: Amelogenesis imperfecta (AI) is defined as inherited enamel malformations. LAMA3 (laminin alpha-3) encodes a critical protein component of the basement membrane (laminin-332). Individuals carrying heterozygous LAMA3 mutations have previously been shown to have localized enamel defects. This study aimed to define clinical phenotypes and to discern the genetic etiology for four AI kindreds.
Materials and methods: Whole exome analyses were conducted to search for sequence variants associated with the disorder, and micro-computed tomography (μCT) to characterize the enamel defects.
Results: The predominant enamel phenotype was generalized thin enamel with defective pits and grooves. Horizonal bands of hypoplastic enamel with chalky-white discoloration and enamel hypomineralization were also observed and demonstrated by μCT analyses of affected teeth. Four disease-causing LAMA3 mutations (NM_198129.4:c.3712dup; c.5891dup; c.7367del; c.9400G>C) were identified. Compound heterozygous MMP20 mutations (NM_004771.4:c.539A>G; c.692C>T) were also found in one proband with more severe enamel defects, suggesting a mutational synergism on disease phenotypes. Further analyses of the AI-causing mutations suggested that both α3A (short) and α3B (long) isoforms of LAMA3 are essential for enamel formation.
Conclusions: Heterozygous LAMA3 mutations can cause generalized enamel defects (AI1A) with variable expressivity. Laminin-332 is critical not only for appositional growth but also enamel maturation.
Açıklama
Anahtar Kelimeler
MMP20, Computed Tomography, Dental Enamel, Junctional Epidermolysis Bullosa, Laminin, Mutation
Kaynak
Oral Diseases
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
29
Sayı
8
Künye
Wang, S. K., Zhang, H., Wang, Y. L., Seymen, F., Koruyucu, M., Simmer, J. P., & Hu, J. C. C. (2022). Phenotypic variability in LAMA3‐associated amelogenesis imperfecta. Oral Diseases, 29(8), 3514-3524.
