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Gnathodiaphyseal dysplasia: report of a family with a novel mutation of the ANO5 gene.

ABSTRACT: Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant disorder characterized by florid osseous dysplasia of the jaws, bone fragility, and diaphyseal cortical thickening and bowing of long bones. We present a family with previously undiagnosed GDD. The disorder was identified by the characteristic gnathic and skeletal manifestations in the father. Clinical and radiologic examination of the patient's son also revealed the characteristic features of GDD. Gene sequencing revealed a novel mutation (c. 1067 G>A, p. Cys356 Tyr) in the ANO5 gene, which is causative for GDD. This mutation was predicted to be detrimental by computational analyses and by structural modeling of the protein. The implications for recognition and management of this disease are discussed.

SUBMITTER: Duong HA

PROVIDER: S-EPMC4830924 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Gnathodiaphyseal dysplasia: report of a family with a novel mutation of the ANO5 gene.

Duong Hannah A HA Le Karen T KT Soulema Albert L AL Yueh Ronald H RH Scheuner Maren T MT Holick Michael F MF Christensen Russell R Tajima Tracey L TL Leung Angela M AM Mallya Sanjay M SM

Oral surgery, oral medicine, oral pathology and oral radiology 20160128 5

Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant disorder characterized by florid osseous dysplasia of the jaws, bone fragility, and diaphyseal cortical thickening and bowing of long bones. We present a family with previously undiagnosed GDD. The disorder was identified by the characteristic gnathic and skeletal manifestations in the father. Clinical and radiologic examination of the patient's son also revealed the characteristic features of GDD. Gene sequencing revealed a novel mut ...[more]

PMID: 27068316

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Gnathodiaphyseal dysplasia: Severe atypical presentation with novel heterozygous mutation of the anoctamin gene (ANO5).

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Novel ANO5 mutation c.1067G>T (p.C356F) identified by whole genome sequencing in a big family with atypical gnathodiaphyseal dysplasia.

Project description:BackgroundGnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied.MethodsSanger sequencing, whole-genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed.ResultsA family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed.ConclusionsThe novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions.

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Gnathodiaphyseal dysplasia is not recapitulated in a respective mouse model carrying a mutation of the Ano5 gene.

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Gain of function of TMEM16E/ANO5 scrambling activity caused by a mutation associated with gnathodiaphyseal dysplasia.

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Autosomal Dominant ANO5-Related Disorder Associated With Myopathy and Gnathodiaphyseal Dysplasia.

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Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies.

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Three novel ANO5 missense mutations in Caucasian and Chinese families and sporadic cases with gnathodiaphyseal dysplasia.

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A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree.

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The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD).

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Novel COL9A3 mutation in a family diagnosed with multiple epiphyseal dysplasia: a case report.

Project description:BACKGROUND: Multiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature, early-onset osteoarthritis mainly involving the hip and knee joints, and abnormally small and/or irregular epiphyses. Multiple epiphyseal dysplasia is clinically and genetically heterogeneous and six genes are associated with the phenotype of multiple epiphyseal dysplasia. CASE PRESENTATION: A 12-year-old Korean boy presented with intermittent knee pain. His height was 144.6 cm (20th percentile) and family history was notable for early-onset osteoarthritis in his father. The proband's x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel c.104G>A substitution in exon 2 of COL9A3, resulting in p.Gly35Asp in the proband and his father. In silico analyses predicted the p.Gly35Asp amino acid change to be detelerious, and molecular dynamics simulation demonstrated a major structural change in the heterotrimeric collagen IX. CONCLUSION: So far, three COL9A3 mutations, have been reported. These three mutations are located at the splice donor or acceptor site of COL9A3 and cause skipping of exon 3, resulting in the deletion of 12 aminoacids in the COL3 domain of COL9A3. In contrast, the novel missense mutation identified in this two-generation family with multiple epiphyseal dysplasia is a missense mutation affecting the Gly residue of the Pro-Pro-Gly repeat sequence in the COL3 domain of collage IX, with accompanying major structural change of the collagen peptide.

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