Clinical, genetic characteristics and treatment outcomes of children and adolescents with osteogenesis imperfecta: a two-center experience

Background: Osteogenesis imperfecta (OI), is a heritable, heterogeneous connective tissue disorder, characterized by fragile bones. There are conflicting results about genotype-phenotype correlations and efficiency of bisphosphonate treatment in this disorder. Aim: We aimed to evaluate the clinical, genetic characteristics, and long-term follow-up results of children and adolescents with OI. Materials and methods: A two-center retrospective study was conducted using demographic, clinical, and genetic data obtained from the medical records of the patients. Results: Twenty-nine patients (62% male, median age; 3.6 years) with OI diagnosis from 26 families were included in the study. Thirteen different variants (nine were novel) were described in 16 patients in COL1A1, COL1A2, and P3H1 genes. Our siblings with homozygous P3H1 variants had a severe phenotype with intrauterine and neonatal fractures. Twenty-two patients were treated with bisphosphonates (17 of them with pamidronate, five with alendronate) with a median duration of 3.0 (1.6-4.8) years. Eleven patients (50%) suffered from fractures after the treatment. Haploinsufficiency variants in COL1A1 caused a milder skeletal phenotype with less fracture count and better treatment outcomes than structural variants. When compared with the anthropometric measurements at the initial diagnosis time, height Z-scores were lower on the last clinical follow-up (p = 0.009). Conclusions: We could not find an obvious genotype-phenotype correlation in Turkish OI patients with COL1A1 or COL1A2 variants. Treatment with pamidronate was effective in reducing fracture counts, without any long-term adverse effects

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease