Amelogenesis imperfecta: A novel FAM83H mutation and characteristics of periodontal ligament cells

Abstract

We identified the novel mutation in FAM83H associated with autosomal dominant hypocalcified AI. The FAM83H cells showed reduced cell proliferation and expression of osteogenic markers, suggesting altered PDLCs in FAM83H-associated AI.

Decreased osteogenic activity and mineralization of alveolar bone cells from a patient with amelogenesis imperfecta and FAM83H 1261G>T mutation

“…2B). Clinical and radiographic features of the proband were described in our previous study 11 . Bone chips were obtained from the proband during osteoplasty according to orthodontic treatment plan.

Figure 1 Clinical and radiographic features of the proband and proliferation of FAM83H mutant cells.

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“…Informed consents were obtained from all participants in this study. Genetic mutation was analyzed by whole exome sequencing as described in our previous study 11 . The identified variant was validated in the proband and other family members by Sanger sequencing.…”

“…Murine ameloblast cell line transfected with Fam83h mutant cDNA (c.1186C > T) exhibited a significant decrease in expression of osteogenic marker genes, namely Runx2 , Alp , and Ocn , corresponding with the reduction of ALP activity 10 . Our previous study demonstrated that the periodontal ligament cells isolated from the ADHCAI patient with FAM83H mutation (p.E421*) showed impaired proliferation and downregulation of OCN , BSP , and COL1 levels after mineralization induction 11 . The teeth affected with ADHCAI also showed reduced mineral density.…”

Precision medicine in Thailand

“…Patients consulted for diagnosis by NGS are from all specialties, including neurologists (Veeravigrom et al, ), dentists (Intarak, Theerapanon, Ittiwut, et al, ; Nowwarote et al, ; Porntaveetus, Nowwarote, et al, b; Porntaveetus, Osathanon, et al, ), orthopedists, endocrinologists (Sangsin, Srichomthong, Pongpanich, Suphapeetiporn, & Shotelersuk, , ), hematologists (Ittiwut et al, ; Ittiwut et al, ), dermatologists (Intarak, Theerapanon, Srijunbarl, et al, ; Panmontha et al, ; Panmontha et al, ), immunologists (Suratannon et al, ), syndromologists (Porntaveetus, Abid, et al, ; Porntaveetus, Srichomthong, Ohazama, Suphapeetiporn, & Shotelersuk, ; Porntaveetus, Theerapanon, Srichomthong, & Shotelersuk, ), biochemical geneticists (Chaiyasap et al, ; Phowthongkum, Ittiwut, & Shotelersuk, ; Porntaveetus, Srichomthong, Suphapeetiporn, & Shotelersuk, ), oncologists (Sahakitrungruang et al, ), and radiologists (Yeetong, Phewplung, Kamolvisit, Suphapeetiporn, & Shotelersuk, ). We have observed a wide range of yields depending on disease groups, recruitment criteria and, very importantly the cooperation of the clinicians and the bioinformaticians.…”

Characterisation of the biochemical and cellular roles of native and pathogenic amelogenesis imperfecta mutants of FAM83H

“…FAM83H has also been reported to be overexpressed in several types of cancers, including colorectal cancer [ 8 , 9 ], hepatocellular carcinoma [ 10 ] and prostate cancer [ 11 ]. Nevertheless, FAM83H is the only FAM83 member implicated in amelogenesis, as mutations in FAM83H have been identified in patients with autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) [ [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] ]. Amelogenesis imperfecta (AI) refers to genetic conditions in which enamel formation is compromised.…”