A novel de novo COL1A1 mutation in a Thai boy with osteogenesis imperfecta born to consanguineous parents

Tongkobpetch, Siraprapa; Limpaphayom, Noppachart; Sangsin, Apiruk; Porntaveetus, Thantrira; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

doi:10.1590/1678-4685-gmb-2016-0033

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…The distribution of glycine mutations along COL1A2 has been associated with the phenotypes and severity of OI (Ben Amor et al, 2011;Tongkobpetch et al, 2017). Clinical features and genetic mutations of the proband and his son indicate the diagnosis of OI type IV.…”

Section: Discussionmentioning

confidence: 99%

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

et al. 2020

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Objectives: To investigate tooth ultrastructure and mutation of two patients in a family affected with osteogenesis imperfecta (OI) type IV and dentinogenesis imperfecta (DGI).Methods: Mutations were detected by whole exome and Sanger sequencing. The permanent second molar obtained from the proband (DGI1) and the primary first molar from his affected son (DGI2) were studied for their color, roughness, mineral density, hardness, elastic modulus, mineral content, and ultrastructure, compared to the controls.Results: Two novel missense COL1A2 variants, c.752C > T (p.Ser251Phe) and c.758G > T (p.Gly253Val), were identified in both patients. The c.758G > T was predicted to be the causative mutation. Pulp cavities of DGI1 (permanent teeth) were obliterated while those of DGI2 (primary teeth) were wide. The patients' teeth had darker and redder colors; reduced dentin hardness; decreased, disorganized, and scattered dentinal tubules and collagen fibers; and irregular dentinoenamel junction (DEJ), compared to controls. Lacunae-like structures were present in DGI2. Conclusions:We reported the novel causative mutation, c.758G > T (p.Gly253Val), in COL1A2 for OI type IV and DGI. The DGI dentin demonstrated inferior mechanical property and ultrastructure, suggesting severe disturbances of dentin formation.These could contribute to fragility and prone to infection of DGI teeth. This study expands phenotypic and genotypic spectra of COL1A2 mutations.

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Section: Discussionmentioning

confidence: 99%

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

et al. 2020

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“…Although many de novo OI cases have previously been described (Maasalu et al., ; Steiner, Adsit, & Basel, ; Tongkobpetch et al., ; Yin et al., ), there does not appear, to date, to have been any description or comparative analysis between de novo and inherited collagen I pathogenic variants. In the current study, data on 146 OI patients with either de novo or inherited COL1A1/2 pathogenic variants were analyzed.…”

Section: Introductionmentioning

confidence: 99%

De novo and inherited pathogenic variants in collagen‐related osteogenesis imperfecta

Zhytnik

Maasalu

Duy

et al. 2019

Molec Gen & Gen Med

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Background Osteogenesis imperfecta (OI) is a rare genetic bone fragility disorder. In the current study, differences between the genotypes and phenotypes of de novo and inherited collagen‐related OI were investigated. Methods A comparative analysis was performed of the genotypes and phenotypes of 146 unrelated inherited and de novo collagen I OI cases from Estonia, Ukraine, and Vietnam. Mutational analysis of the subjects and all available parents were performed with Sanger sequencing. Results Results showed that 56.16% of the OI cases were caused by de novo pathogenic variants. The proportion of OI types OI1, OI4, and OI3 among subjects with inherited OI was 45.31%, 46.88%, and 7.81%, respectively. Among subjects with de novo OI, the proportions of OI types (OI1, OI4, and OI3) were almost equal. Both inherited and de novo OI pathogenic variants occurred more often in the COL1A1 gene than in the COL1A2 . The majority of de novo cases were missense pathogenic variants, whereas inherited OI was mostly caused by loss of function pathogenic variants. Conclusion In summary, there were significant differences between the phenotypes and genotypes of subjects with de novo and inherited OI. These findings may promote the further understanding of OI etiology, and assist with diagnostics procedures, as well as with family planning.

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“…Genotype-phenotype correlation gives clues to general developmental biology and is important for genetic counseling 25, 26. It has been shown that the mutations affecting glycine residues in the Gly-X-Y triplet domain of the type I collagen triple helix, compared with haploinsufficiency mutations, are responsible for more severe phenotypes including extensive skeletal abnormalities, low bone mineral density, short stature, dentinogenesis imperfecta, and scoliosis 27, 28.…”

Section: Discussionmentioning

confidence: 99%

A novel mutation in COL1A2 leads to osteogenesis imperfecta/Ehlers-Danlos overlap syndrome with brachydactyly

et al. 2019

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Osteogenesis imperfecta (OI) is mainly characterized by bone fragility and Ehlers-Danlos syndrome (EDS) by connective tissue defects. Mutations in COL1A1 or COL1A2 can lead to both syndromes. OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type I procollagen. In this study, we identified a Thai patient having OI type III, EDS, brachydactyly, and dentinogenesis imperfecta. His dentition showed delayed eruption, early exfoliation, and severe malocclusion. For the first time, ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion, bone-like dentin, loss of dentinal tubules, and reduction in hardness and elasticity, suggesting severe developmental disturbance. These severe dental defects have never been reported in OI or EDS. Exome sequencing identified a novel de novo heterozygous glycine substitution, c.3296G > A, p.Gly1099Glu, in exon 49 of COL1A2 . Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage. Notably, two of these three patients did not show hyperextensible joints and hypermobile skin, while our patient at the age of 5 years had not developed intracranial hemorrhage. Here, we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(I) collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects, expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.

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A novel de novo COL1A1 mutation in a Thai boy with osteogenesis imperfecta born to consanguineous parents

Cited by 6 publications

References 19 publications

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

De novo and inherited pathogenic variants in collagen‐related osteogenesis imperfecta

A novel mutation in COL1A2 leads to osteogenesis imperfecta/Ehlers-Danlos overlap syndrome with brachydactyly

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