ESPE Abstracts (2014) 82 P-D-1-3-50

Genetic Study of Osteogenesis Imperfecta: Two Novel Mutations in COL1A1 and COL1A2

Lidia Castro-Feijóoa, Lourdes Loidib, Nuria Quirogac, Paloma Cabanasd, Claudia Herediad, Rosaura Leise, Francisco Barrosb, Manuel Pombod & Jesús Barreirod


aUnidad de Endocrinología Pediátrica y Crecimiento, Dpto. de Pediatría, Fundación Ramón Domínguez, Hospital Clínico Universitario de Santiago de Compostela, Universidad de Santiago de Compostela, Santiago de Compostela. A Coruña, Spain; bFundación Pública Galega de Medicina Xenómica, Santiago de Compostela, A Coruña, Spain, cDpto de Pediatría, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; dUnidad de Endocrinología Pediátrica y Crecimiento, Dpto de Pediatría, Hospital Clínico Universitario de Santiago de Compostela, Universidad de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain; eUnidad de Investigación en Nutrición y Desarrollo Humano de Galicia, Dpto de Pediatría, Hospital clínico Universitario de Santiago de Compostela, Universidad de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain


Background: Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous rare disorder characterized by variable symptoms including predisposition to fractures. OI has been associated with mutations affecting the synthesis of type I collagen. However, the new technologies have permitted the identification of other responsible genes which are in the collagen metabolic pathway, while others are not.

Objective: Characterize the genotype of patients with OI.

Methods: Study by Next Generation Sequencing (5500XL SOLID) the OI related genes: COL1A1, COL1A2, CRTAP, FKBP10, LEPRE1, PPIB, SERPINF1, SERPINH1 and SP7 and confirmation of the identified mutations by PCR and Sanger sequencing.

Results and discussion: Patient 1 (male with severe phenotype of OI). Heterozygous carrier of the COL1A2 mutation NM_000089.3: c.1207G >T (p.Gly403Cys). This mutation has not been previously described. The theoretical predictors suggest pathogenicity, which is consistent with the clear phenotype of OI in this patient. Patient 2 (girl with mild phenotype of OI). Heterozygous carrier of the COL1A1 mutation NM_000088.3: c.572G > C (p.Gly191Ala). This mutation appears in The Human Gene Mutation Database associated with cervical artery dissection and the missense predictions indicate pathogenicity. Patients 3 and 4 (siblings with moderate phenotype of OI). Both girls are heterozygous carriers of the COL1A1 mutation NM_000088.3: c.2T > C (p.Met1?). This mutation has not been previously described and there is not data of associated phenotype. This variation affects the translation initiation codon of the mRNA which indicates pathogenicity.

Conclusion: The genetic analysis confirmed the diagnosis of OI in all the patients studied. These results allowed a better classification of patients and permitted an adequate genetic counselling. One COL1A1 and one COL1A2 novel mutations are described.

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