Spondiloepi (meta) fizyal displazi ön tanili beş türk erkek hastadaki genetik etyolojinin araştirilmasi

OBJECTIVE: Skeletal dysplasias is a complex disease group characterized by disproportionate short stature and various orthopedic complications. X-Linked Spondyloepiphyseal Dysplasia Tarda is an X-linked inherited skeletal dysplasia accompanied by progressive spondyloepi(meta)physeal dysplasia and premature osteoartritis. The gene related to the disorder is trafficking protein particle complex 2 (TRAPPC2). Progressive pseudorheumatoid dysplasia (PPRD) is characterized by enlargement of the elbow joints and arthritis-like findings. It is an autosomal recessive subtype of skeletal dysplasia caused by mutations in cellular communication network factor 6 (CCN6) gene located on chrosomal region 6q21. In this study, it was aimed to diagnose five male individuals with an X-linked or autosomal recessive inheritance pattern, who have not been diagnosed for years, to identify possible treatments and to offer prenatal pmreimplantation genetic testing. MATERIAL AND METHODS: Five male siblings with skeletal dysplasia with an uncertain inheritance either X-linked or autosomal recessive pattern were included in this study, Whole Exome Sequencing (WES) was applied to the four affected cases. Sanger Sequencing was performed in one affected case and four healthy individuals. RESULTS: Homozygous c.210C>A (p.Cys70Ter) and homozygous c.302G>A (p.Gly101Glu) mutations in the CCN6 gene were found in all affected siblings. Thus, the final diagnosis after WES was autosomal recessive PPRD despite the possibility of an X-linked recessive pattern. CONCLUSIONS: This study presents a series of the oldest patients diagnosed with Progressive pseudorheumatoid dysplasia, normally a childhood disease, with an average age of 54.6. The p.Cys70Ter alteration is the most frequent pathogenic variant in Turkish patients. This study is also important in terms of showing that Progressive pseudorheumatoid dysplasia has no significant effect on life expectancy. At the same time, this study shows the progression of this disease and clinical findings that may accompany lifetime.