Gastrointestinal symptoms in patients with isolated oligodontia and a Wnt gene mutation

OBJECTIVE: Since Wnt signaling plays an important role in both tooth agenesis and altered intestine homeostasis, the aim was to compare gastrointestinal symptoms in patients with isolated oligodontia caused by a Wnt pathway gene mutation and controls. METHODS: A case-control study was designed to compare self-reported gastrointestinal symptoms among patients with isolated oligodontia, caused by a Wnt signaling gene mutation, and fully dentate controls. The Gastrointestinal Symptom Rating Scale (GSRS) was used to assess gastrointestinal symptoms. Prevalence and severity of gastrointestinal symptoms among patients and age- and gender-matched controls was evaluated. RESULTS: Twenty patients with isolated oligodontia and a pathogenic variant in the wnt pathway genes WNT10A, LRP6 or PAX9 participated. The prevalence of gastrointestinal symptoms was higher in the oligodontia patients compared to their controls (Χ2 (1) = 87.33, p = .008). Mean GSRS total scores (p = .011) and domain scores for 'abdominal pain' (p = .022), 'reflux' (p = .003) and constipation (p = .030) were higher for these oligodontia patients compared to their controls. CONCLUSION: Gastrointestinal symptoms are more prevalent and more severe in patients with isolated oligodontia and a deficiency in a Wnt pathway related gene, when compared to controls without tooth agenesis

Oral Health-Related Quality of Life in Dutch Children Diagnosed with Oligodontia. A Cross-Sectional Study

There is need to get insight into condition-specific oral health-related quality of life in Dutch children with oligodontia. Between October 2014 and March 2017, 11-17-year-old oligodontia patients were approached to join a study assessing the impact of oligodontia on condition-specific oral health-related quality of life (OHrQoL). The patients received a condition-specific OHrQoL questionnaire prior to the start of orthodontic treatment. Non-oligodontia children in the same age group, but also requiring orthodontic treatment, were approached to serve as a control. The Fisher's Exact Test was used for comparison purposes with the control group because of the small group sizes. Furthermore, subgroup analyses were performed for gender, age, number of congenitally missing teeth, tooth agenesis in the aesthetic region, orthodontic classification and microdontia via independent t-tests. p-values of <0.05 were considered statistically significant. Twenty-eight oligodontia patients and 23 controls agreed to participate. The oligodontia patients' scores were comparable to the controls except for the items about dental appearance and treatment complexity. The impact of oligodontia on OHrQoL in youngsters is limited and mainly concerns dental appearance and the complexity of the treatment

Concurrent manifestation of oligodontia and thrombocytopenia caused by a contiguous gene deletion in 12p13.2 : A three-generation clinical report

Background: Wnt and Wnt-associated pathways play an important role in the genetic etiology of oligodontia, a severe form of tooth agenesis. Loss-of-function mutations in LRP6, encoding a transmembrane cell-surface protein that functions as a coreceptor in the canonical Wnt/b-catenin signaling cascade, also contribute to genetic oligodontia. Methods and results: We describe a three-generation family with hereditary thrombocytopenia and oligodontia. Genome wide array analysis was performed. The array results from the index patient revealed an interstitial loss of 150 kb in 8p23.1 (chr8:6,270,299–6,422,558; hg19) encompassing MCPH1 and ANGPT2 and an interstitial loss of 290 kb in 12p13.2 (chr12:12,005,720–12,295,290; hg19) encompassing ETV6, BCL2L14 and LRP6. Conclusion: This case report shows a three-generation family with hereditary thrombocytopenia and oligodontia with a heterozygous 290 kb novel contiguous gene deletion in band p13.2 of chromosome 12, encompassing LRP6 and ETV6. In this report we discuss the clinical relevance of the deletion of both genes and illustrate the importance of thorough examination of oligodontia patients. Comprising not only the oral status but also the medical history of the patients and their relatives

Concurrent manifestation of oligodontia and thrombocytopenia caused by a contiguous gene deletion in 12p13.2: A three-generation clinical report

BACKGROUND: Wnt and Wnt-associated pathways play an important role in the genetic etiology of oligodontia, a severe form of tooth agenesis. Loss-of-function mutations in LRP6 , encoding a transmembrane cell-surface protein that functions as a coreceptor in the canonical Wnt/b-catenin signaling cascade, also contribute to genetic oligodontia. METHODS AND RESULTS: We describe a three-generation family with hereditary thrombocytopenia and oligodontia. Genome wide array analysis was performed. The array results from the index patient revealed an interstitial loss of 150 kb in 8p23.1 (chr8:6,270,299-6,422,558; hg19) encompassing MCPH1 and ANGPT2 and an interstitial loss of 290 kb in 12p13.2 (chr12:12,005,720-12,295,290; hg19) encompassing ETV6, BCL2L14 and LRP6. CONCLUSION: This case report shows a three-generation family with hereditary thrombocytopenia and oligodontia with a heterozygous 290 kb novel contiguous gene deletion in band p13.2 of chromosome 12, encompassing LRP6 and ETV6. In this report we discuss the clinical relevance of the deletion of both genes and illustrate the importance of thorough examination of oligodontia patients. Comprising not only the oral status but also the medical history of the patients and their relatives

Gastrointestinal symptoms in patients with isolated oligodontia and a Wnt gene mutation

OBJECTIVE: Since Wnt signaling plays an important role in both tooth agenesis and altered intestine homeostasis, the aim was to compare gastrointestinal symptoms in patients with isolated oligodontia caused by a Wnt pathway gene mutation and controls. METHODS: A case-control study was designed to compare self-reported gastrointestinal symptoms among patients with isolated oligodontia, caused by a Wnt signaling gene mutation, and fully dentate controls. The Gastrointestinal Symptom Rating Scale (GSRS) was used to assess gastrointestinal symptoms. Prevalence and severity of gastrointestinal symptoms among patients and age- and gender-matched controls was evaluated. RESULTS: Twenty patients with isolated oligodontia and a pathogenic variant in the wnt pathway genes WNT10A, LRP6 or PAX9 participated. The prevalence of gastrointestinal symptoms was higher in the oligodontia patients compared to their controls (Χ2 (1) = 87.33, p = .008). Mean GSRS total scores (p = .011) and domain scores for 'abdominal pain' (p = .022), 'reflux' (p = .003) and constipation (p = .030) were higher for these oligodontia patients compared to their controls. CONCLUSION: Gastrointestinal symptoms are more prevalent and more severe in patients with isolated oligodontia and a deficiency in a Wnt pathway related gene, when compared to controls without tooth agenesis

Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia

RNA polymerase III (Pol III) is an essential 17-subunit complex responsible for the transcription of small housekeeping RNAs such as transfer RNAs and 5S ribosomal RNA. Biallelic variants in four genes (POLR3A, POLR3B, and POLR1C and POLR3K) encoding Pol III subunits have previously been found in individuals with (neuro-) developmental disorders. In this report, we describe three individuals with biallelic variants in POLR3GL, a gene encoding a Pol III subunit that has not been associated with disease before. Using whole exome sequencing in a monozygotic twin and an unrelated individual, we detected homozygous and compound heterozygous POLR3GL splice acceptor site variants. RNA sequencing confirmed the loss of full-length POLR3GL RNA transcripts in blood samples of the individuals. The phenotypes of the described individuals are mainly characterized by axial endosteal hyperostosis, oligodontia, short stature, and mild facial dysmorphisms. These features largely fit within the spectrum of phenotypes caused by previously described biallelic variants in POLR3A, POLR3B, POLR1C, and POLR3K. These findings further expand the spectrum of POLR3-related disorders and implicate that POLR3GL should be included in genetic testing if such disorders are suspected

Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia

RNA polymerase III (Pol III) is an essential 17-subunit complex responsible for the transcription of small housekeeping RNAs such as transfer RNAs and 5S ribosomal RNA. Biallelic variants in four genes (POLR3A, POLR3B, and POLR1C and POLR3K) encoding Pol III subunits have previously been found in individuals with (neuro-) developmental disorders. In this report, we describe three individuals with biallelic variants in POLR3GL, a gene encoding a Pol III subunit that has not been associated with disease before. Using whole exome sequencing in a monozygotic twin and an unrelated individual, we detected homozygous and compound heterozygous POLR3GL splice acceptor site variants. RNA sequencing confirmed the loss of full-length POLR3GL RNA transcripts in blood samples of the individuals. The phenotypes of the described individuals are mainly characterized by axial endosteal hyperostosis, oligodontia, short stature, and mild facial dysmorphisms. These features largely fit within the spectrum of phenotypes caused by previously described biallelic variants in POLR3A, POLR3B, POLR1C, and POLR3K. These findings further expand the spectrum of POLR3-related disorders and implicate that POLR3GL should be included in genetic testing if such disorders are suspected