New heritable ATRX mutation identified by whole exome sequencing and review

Abstract

Background ATRX gene encodes a member of the SWI2/SNF2 family of proteins that may act as a transcriptional factor and plays a significant role in the epigenetic regulation of gene expression. The mutations in the ATRX gene have been shown to cause two types of disorders: inherited mutations lead to alpha thalassemia X-linked mental retardation (ATR-X) syndrome and acquired somatic mutations cause alpha thalassemia myelodysplastic syndrome (ATMDS). Here we report a case of ATRX gene mutation without completely features of ATR-X or ATMDS syndromes. Moreover we review previous reports of ATRX gene mutations in both ATR-X syndrome and ATMDS. Methods Patient was a 29-year-old male of Arab ancestry with normocytic anemia, low mean corpuscular hemoglobin (MCH), haematocrit percent and red blood cell (RBC) count. He had no sign of mental retardation and facial dysmorphism. The whole exome sequencing method was used to find the disease-causing variants. Moreover we searched HGMD, Ensembl, OMIM and COSMIC databanks for all mutation reported in ATRX gene so far, and Pubmed, WOS, Science direct and springer link for articles that reported ATRX gene mutations. Results We identified a hemizygous missense ATRX gene mutation ( ATRX, c.2388A>C, p. K796N) as a new disease-causing variant in the patient. Conclusion According to previous findings, inherited ATRX mutations are associated with a broad spectrum of clinical presentations. Therefore a person with a mild α-thalassemia phenotype may also have mutation in ATRX gene. Accordingly, it is critical for geneticist and physicians to increase awareness in molecular diagnosis of α-thalassemia patients.