The diagnosis and molecular analysis of a novel 27.2 kb deletion causing α0-thalassemia.

BACKGROUND: Thalassemia, one of the most prevalent monogenic diseases worldwide, is caused by an imbalance of α-like and non-α-like globin chain production. Copy number variations, which cause the most common genotype of α-thalassemia, can be detected by multiple diagnostic methods. CASE REPORT: The proband was a 31-year-old female who was diagnosed with microcytic hypochromic anemia by antenatal screening. Hematological analysis and molecular genotyping were conducted on the proband and the proband's family members. Gap-polymerase chain reaction, Sanger sequencing, multiplex ligation-dependent probe amplification, and next-generation sequencing were used to detect potentially pathogenic genes. Familial studies and genetic analyses revealed a novel deletion of 27.2 kb located in the α-globin gene cluster (NC_000016.9: g. 204538_231777delinsTAACA). CONCLUSIONS: We reported a novel α-thalassemia deletion and described the process of molecular diagnosis. The novel deletion extends the thalassemia mutation spectrum, which may be helpful in genetic counseling and clinical diagnosis in the future.

Diamond-Blackfan anaemia caused by a de novo initiation codon mutation resulting in a shorter isoform of GATA1.

Diamond-Blackfan anaemia (DBA) is an inherited marrow failure disorder characterised by selective erythroid aplasia. Herein, we reported a case of DBA caused by a novel GATA1 gene mutation. The proband manifested normocytic normochromic anaemia, while the parents were asymptomatic. Next-generation sequencing identified a novel de novo mutation at GATA1 initiation codon (GATA1:c.3G>A) in the proband. The mutation led to a shortened GATA1 protein (GATA1s), which caused a reduction in full-length functional GATA1 protein (GATA1fl). This is the first report of GATA1-related DBA patient in the East Asian population, which expanded the mutational spectrum of DBA furthering understanding of its pathogenesis.