A Novel ATRX Mutation Presenting with Intellectual Disability and Severe Kyphoscoliosis

Abstract

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.

Keywords:

• ATR-X Syndrome
• ATRX
• XH2
• kyphoscoliosis

Acknowledgment

The authors thank to the family for their collaboration for this publication.

Statement of ethics

The authors have no ethical conflicts to disclose.

Disclosure statement

No potential conflict of interest was reported by the authors.