Dental radiographic findings in 18 individuals with SATB2-associated syndrome

Scott, John M.; Adams, Chad; Simmons, Katharine B.; Feather, Andrea; Jones, John; Hartzell, Larry; Wesley, Lucia; Johnson, Adam B.; Fish, Jennifer L.; Bosanko, Katherine A.; Beetstra, Stephen; Zárate, Yuri A.

doi:10.1007/s00784-018-2702-9

Cited by 10 publications

(12 citation statements)

References 17 publications

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“…Tables detail all 101 previously published SATB2 intragenic alterations in the international peer‐reviewed literature (PubMed database) and the Human Gene Mutation Database (HGMD professional 2018.3; Brewer et al, ; Leoyklang et al, ; Baptista et al, ; Rosenfeld et al, ; Tegay et al, ; Balasubramanian et al, ; Rauch et al, ; Talkowski et al, ; Asadollahi et al, ; Gilissen et al, ; Lieden, Kvarnung, Nilssson, Sahlin, & Lundberg, ; Rainger et al, ; Trakadis et al, ; Farwell et al, ; Kaiser et al, ; Zarate et al, ; Boone et al, ; Lee et al, ; Bengani et al, ; Bowling et al, ; Deciphering Developmental Disorders Study, ; Schwartz, Wilkens, Noon, Krantz, & Wu, ; Vissers et al, ; Zarate et al, ; Cherot et al, ; Kikuiri et al, ; Lv et al, ; Scott et al, ; Zarate, Smith‐Hicks et al, ; Zarate, Steinraths et al, ). In this study, we also report 57 additional individuals with 47 SATB2 alterations (Tables ) that have been submitted to the LOVD database: https://databases.lovd.nl/shared/genes/SATB2.…”

Section: Variantsmentioning

confidence: 99%

“…Intellectual disability has been reported in several individuals old enough to undergo cognitive evaluations and often in the moderate to severe range (Zarate, Smith‐Hicks et al ()). Dental abnormalities are present in all individuals and include delayed development of the mandibular second bicuspids or the roots of the permanent teeth, severely rotated or malformed teeth, taurodontism, and multiple odontomas (Kikuiri et al, ; Scott et al, ). Behavioral difficulties, feeding issues, abnormal brain neuroimaging, low bone density, suggestive facial features, and cleft palate complete the characteristic phenotype of SAS (Table ).…”

Section: Clinical and Diagnostic Relevancementioning

confidence: 99%

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Mutation update for the SATB2 gene

et al. 2019

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SATB2‐associated syndrome (SAS) is an autosomal dominant neurodevelopmental disorder caused by alterations in the SATB2 gene. Here we present a review of published pathogenic variants in the SATB2 gene to date and report 38 novel alterations found in 57 additional previously unreported individuals. Overall, we present a compilation of 120 unique variants identified in 155 unrelated families ranging from single nucleotide coding variants to genomic rearrangements distributed throughout the entire coding region of SATB2. Single nucleotide variants predicted to result in the occurrence of a premature stop codon were the most commonly seen (51/120 = 42.5%) followed by missense variants (31/120 = 25.8%). We review the rather limited functional characterization of pathogenic variants and discuss current understanding of the consequences of the different molecular alterations. We present an expansive phenotypic review along with novel genotype‐phenotype correlations. Lastly, we discuss current knowledge of animal models and present future prospects. This review should help provide better guidance for the care of individuals diagnosed with SAS.

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Section: Variantsmentioning

confidence: 99%

Section: Clinical and Diagnostic Relevancementioning

confidence: 99%

Mutation update for the SATB2 gene

et al. 2019

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“…For the dental phenotypes of SAS patients, regardless of genotype, the most consistent features include macrodontia, crowded dentition, delayed tooth eruption, and delayed root formation of the permanent tooth [7,8]. This report presents dental phenotypes including malocclusion, crowded dentition, larger-than-normal teeth, malposed teeth, talon cusp, extensive caries and poor oral hygiene.…”

Section: Discussionmentioning

confidence: 86%

“…For palatal and dental abnormalities, clinical manifestations include cleft palate, high-arched palate, macrodontia, delayed tooth eruption, malformed teeth, missing teeth, sialorrhea, and bruxism [7,8]. However, there are few reports about the dental phenotype of primary dentition.…”

Section: Introductionmentioning

confidence: 99%

The dental phenotype of primary dentition in SATB2-associated syndrome: a report of three cases and literature review

2022

BMC Oral Health

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Background SATB2-associated syndrome (SAS; OMIM: 612,313) is an autosomal dominant inherited multisystemic disorder caused by several variants of the SATB2 gene. SAS is characterized by intellectual disability, developmental delay, severe speech anomalies, craniofacial anomalies, and dental abnormalities. Here, we report the dental phenotype of primary dentition of three Chinese children with SAS. Case presentation All three cases with SAS showed intellectual disability, speech and language anomalies, and palate anomalies. For the dental phenotype, all three cases showed macrodontia, crowded dentition, extensive caries, periapical abscesses and fistulas. Radiographs showed the wide-open root apex of deciduous teeth, loss of mandibular second bicuspids, delayed root formation of permanent teeth, rotated teeth, and taurodontism. Sanger sequencing of case 1 showed that there was a heterozygous code shift variation, c1985delT (p.F662Sfs*9) in the SATB2 gene, which has not been reported in literature. Root canal therapy, carious restoration, and teeth extraction were managed promptly, while preventive dental care was given regularly. Conclusions The dental phenotype of primary dentition in SAS may show macrodontia, crowded dentition, severe caries, wide-open root apex of deciduous teeth, loss of mandibular second bicuspids, delayed root formation of permanent teeth, rotated teeth, and taurodontism. Regular oral hygiene instructions and preventive dental care are both required.

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“…Function enhancement of hDPSCs by activating Wnt/ β -catenin signaling pathway or through JHDM1D-induced epigenetic modulation may be considered as new therapeutic strategies for SAS patients with the manifestation of tooth agenesis. Since SAS patients exhibit defects of multiple organs, current treatment strategies are mainly symptom-guided [ 10 , 33 , 51 , 52 ]. Underlying cellular and molecular pathogenic mechanism of SAS needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway

Xin¹,

Li²,

Bai³

et al. 2021

Stem Cell Res Ther

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Background SATB2-associated syndrome (SAS) is a multisystem disorder caused by mutation of human SATB2 gene. Tooth agenesis is one of the most common phenotypes observed in SAS. Our study aimed at identifying novel variant of SATB2 in a patient with SAS, and to investigate the cellular and molecular mechanism of tooth agenesis caused by SATB2 mutation. Methods We applied whole exome sequencing (WES) to identify the novel mutation of SATB2 in a Chinese patient with SAS. Construction and overexpression of wild-type and the mutant vector was performed, followed by functional analysis including flow cytometry assay, fluorescent immunocytochemistry, western blot, quantitative real-time PCR and Alizarin Red S staining to investigate its impact on hDPSCs and the underlying mechanisms. Results As a result, we identified a novel frameshift mutation of SATB2 (c. 376_378delinsTT) in a patient with SAS exhibiting tooth agenesis. Human DPSCs transfected with mutant SATB2 showed decreased cell proliferation and odontogenic differentiation capacity compared with hDPSCs transfected with wild-type SATB2 plasmid. Mechanistically, mutant SATB2 failed to translocate into nucleus and distributed in the cytoplasm, failing to activate Wnt/β-catenin signaling pathway, whereas the wild-type SATB2 translocated into the nucleus and upregulated the expression of active β-catenin. When we used Wnt inhibitor XAV939 to treat hDPSCs transfected with wild-type SATB2 plasmid, the increased odontogenic differentiation capacity was attenuated. Furthermore, we found that SATB2 mutation resulted in the upregulation of DKK1 and histone demethylase JHDM1D to inhibit Wnt/β-catenin signaling pathway. Conclusion We identified a novel frameshift mutation of SATB2 (c.376_378delinsTT, p.Leu126SerfsX6) in a Chinese patient with SATB2-associated syndrome (SAS) exhibiting tooth agenesis. Mechanistically, SATB2 regulated osteo/odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway by regulating DKK1 and histone demethylase JHDM1D.

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Dental radiographic findings in 18 individuals with SATB2-associated syndrome

Cited by 10 publications

References 17 publications

Mutation update for the SATB2 gene

Mutation update for the SATB2 gene

The dental phenotype of primary dentition in SATB2-associated syndrome: a report of three cases and literature review

A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway

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