A Novel ATRX Mutation Presenting with Intellectual Disability and Severe Kyphoscoliosis

Background: ATR-X syndrome is an X-linked clinical condition usually associated with profound intellectual disability, facial dysmorphism and alpha-thalassemia. The syndrome is clinically heterogeneous with a broad phenotypic spectrum. Although, alpha-thalassaemia is commonly present, it may not manifest in some patients.Case report: A novel missence mutation (NM_000489: ATRX; c.6130C > T; p.Leu2044Phe) was detected in the ATR-X gene in two male siblings with severe intellectual disability, dysmorphic facial appearance and skeletal anomalies. Severe kyphoscoliosis was the main finding. Hematologic findings, one of the well-known clinical entities, were not present.Conclusion: The missense mutation we have described in our patients has not been previously reported. This finding enriches mutation spectrum of ATRX (OMIM #300032) gene. This missense mutation, which is associated with ID and kyphoscoliosis and without alpha-thalassemia, contributes to genotype-phenotype correlation of the ATR-X spectrum. This case report provides further evidence that reverse genetics is a useful approach in diagnostic process of syndromic patients in adulthood.