ESPE Abstracts (2016) 86 P-P1-131

Frequency of Recessive Osteogenesis Imperfecta in a Turkish Cohort and Genetic Causes

Saygin Abalia, Ahmet Armanb, Zeynep Ataya, Abdullah Bereketa, Serpil Basa, Belma Haliloglua, Tulay Gurana, Zeliha Gormezc, Huseyin Demircic, Nurten Akarsud & Serap Turana

aPediatric Endocrinology, Marmara University, School of Medicine, Istanbul, Turkey; bMedical Genetics, Marmara University, School of Medicine, Istanbul, Turkey; cAdvanced Genomics and Bioinformatics Research Center TUBITAK-BILGEM-UEKAE, Kocaeli, Turkey; dMedical Genetics, Hacettepe University, School of Medicine, Ankara, Turkey

Background: Osteogenesis imperfecta (OI) is a heterogeneous group of brittle bone disease mostly caused by quantative or qualitative defects in type I collagen. In most populations, more than 90% of the patients with OI have dominant mutations in COL1A1 or COL1A2 genes (AD-OI). Less than 10% of the cases have recessive inheritance (AR-OI). Currently 12 genes have been identified as a cause of AR-OI.

Objective and hypotheses: We assumed higher frequency of AR-OI in our population because of high consanguineous marriages and aimed to detect AR-OI rate and distribution of genetic causes in our cohort.

Method: Eighty-nine patients from 73 families were evaluated for inclusion. The patients having parental OI history (27 families) and/or patients with mutations in COL1A genes (5 families) were excluded because of AD-OI. The patients born to consanguineous parents were included as AR-OI (29 patients/25 families). In AR-OI group, two patients had osteoporosis-pseudoglioma and five patients (four families) had epidermolysis bullosa and found to have founder mutation of p.delGly107_Leu117del in FKBP10 gene. Remaining 19 families were called for genetic analyses. Three patients were died. Whole exome sequencing (WES) was performed to seven index patients.

Results: Novel mutations in LEPRE1, CRTAP and FKBP10 genes were detected in WES We also detected a nonsense mutation in SPARC in two siblings which is a newly described AR-OI gene. Two cousins with severe platyspondily had mutation in BMP1 gene. The other two index cases are still under investigation. Overall, the frequency of recessive OI was 34.2% of the families and 32.6% of the patients.

Conclusion: In our cohort of OI, 1/3 of patients have AR-OI. In 11 families with genetic results, five FKBP10, two LRP5, and one each LEPRE1, CRTAP, BMP1 and SPARC gene mutation have been detected. Distribution of mutations seem to differ from AR-OI cohorts of Spain (n:10) and India (n:7).