New heritable ATRX mutation identified by whole exome sequencing and review

Zahra Shahbazi,Mohammad Hamid,Golaleh Rostami

doi:10.1186/s43042-022-00227-7

Abstract

BackgroundThe 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.MethodsAfter sample collection and DNA extraction, whole exome sequencing was performed using Illumina HiSeq PE150 apparatus. The results were confirmed using Sanger sequencing for the patients and his relatives. Literature review was performed based on the published data in Web of science, Science direct, Springer link and Pubmed databases.ResultsWe identified a hemizygous missense ATRX gene mutation (ATRX, c.2388A > C, p. K796N) as a new disease-causing variant in the patient, heterozygous situation for his mother and his father was hemizygous for wild type allele. The literatures of patients were reviewed regarding the ATR-X syndrome.ConclusionsAccording 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 has mutation in ATRX gene. Accordingly, it is critical for geneticist and physicians to increase awareness in molecular diagnosis of α-thalassemia patients.

Highlights

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)
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders characterized by peripheral blood cytopenias and microcytic red blood cell (RBC) indices in the absence of iron deficiency as a result of ineffectual erythropoiesis [1, 2]
A proband 29-year-old male with 167 cm height referred because of gastrointestinal signs, was found to have normocytic anemia (low hemoglobin (Hgb) (5.6 g/dl), low mean corpuscular hemoglobin (MCH) (26.8 pg) and haematocrit percent (18.3%). He was normal for some quantities including mean corpuscular volume (MCV) (96.4fL), white blood cell (WBC) count (4.3 × 103/mm3), platelet count (PLT) (199 × 103/mm3) and lymphocyte, monocyte, eosinophil, basophil percent (36.9%, 4.5%, 0.8%, 0.2 respectively)

Summary

Introduction

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). The ATRX gene encodes a member of the SWI2/SNF2 (Switching defective/Sucrose nonfermenting) family of proteins [5] that may act as a transcriptional factor and plays a significant role in the epigenetic regulation of gene expression [6]. The unusual α-thalassemia and microcytosis in the ground of MDS is due to a decreased synthesis of α-globin related to a dramatic down regulation of α-globin gene expression by inactivating mutation in the ATRX gene [7]. On the other hand, inherited mutations in the ATRX gene, have been shown to cause an alpha thalassemia X-linked mental retardation (ATR-X)

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