Gnathodiaphyseal dysplasia: Severe atypical presentation with novel heterozygous mutation of the anoctamin gene (ANO5)
Autor: | Ghada A. Otaify, Marina Stolina, Marwan Shinawi, Olivier Lichtarge, Abby S. Hollander, Wei-Shen Chen, Samir K. El-Mofty, J. Eric Gordon, Albert S. Woo, Gary S. Gottesman, Michael P. Whyte, Marisa V. Andrews, William H. McAlister, Panagiotis Katsonis, Fan Zhang, Deborah V. Veis |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Diaphyseal sclerosis Pathology medicine.medical_specialty Histology Physiology Gnathodiaphyseal dysplasia Endocrinology Diabetes and Metabolism Mutation Missense Anoctamins Article 03 medical and health sciences Exon medicine Humans Missense mutation Genetics business.industry Osteogenesis Imperfecta Debulking medicine.disease Cherubism Phenotype 030104 developmental biology Child Preschool Maxilla Mutation (genetic algorithm) business |
Zdroj: | Bone. 107:161-171 |
ISSN: | 8756-3282 |
Popis: | Gnathodiaphyseal dysplasia (GDD; OMIM #166260) is an ultra-rare autosomal dominant disorder caused by heterozygous mutation in the anoctamin 5 (ANO5) gene and features fibro-osseous lesions of the jawbones, bone fragility with recurrent fractures, and bowing/sclerosis of tubular bones. The physiologic role of ANO5 is unknown. We report a 5-year-old boy with a seemingly atypical and especially severe presentation of GDD and unique ANO5 mutation. Severe osteopenia was associated with prenatal femoral fractures, recurrent postnatal fractures, and progressive bilateral enlargement of his maxilla and mandible beginning at ~ 2 months-of-age that interfered with feeding and speech and required four debulking operations. Histopathological analysis revealed benign fibro-osseous lesions resembling cemento-ossifying fibromas of the jaw without psammomatoid bodies. A novel, de novo, heterozygous, missense mutation was identified in exon 15 of ANO5 (c.1553G>A; p.Gly518Glu). Our findings broaden the phenotypic and molecular spectra of GDD. Fractures early in life with progressive facial swelling are key features. We assessed his response to a total of 7 pamidronate infusions commencing at age 15 months. Additional reports must further elucidate the phenotype, explore any genotype-phenotype correlation, and evaluate treatments. |
Databáze: | OpenAIRE |
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