Identification of a Novel 7-bp Deletion in the α-Globin Gene Cluster in One Chinese Family.

Deletional α-thalassemia is characterized by reduced hemoglobin A2 and involves the deletion of a few nucleotides, which is a rare hereditary disease. However, the detection of rare mutations using commonly used genetic tests is highly challenging. In the present study, next-generation sequencing (NGS) was used to identify a novel 7-bp deletion α-thalassemia in one individual from a Chinese family. Hematological parameters of the family members were determined using an automated cell counter, and hemoglobin electrophoresis was performed using a capillary electrophoresis system. Subsequently, NGS was performed on the genomic DNA of the patient and her family members. The 7-bp deletion (named Hb Honghe [HBA1: c.401_407delGCACCGT]) of α-thalassemia in the α-globin gene was confirmed using Sanger sequencing. The patient's father was also a heterozygous carrier of HBA1: c.401_407delGCACCGT deletion, but not her mother or sister. The application of the combined molecular approach is essential for the accurate diagnosis of rare thalassemia. This study reports a novel case of α- thalassemia. The characterization of the mutation might provide new insights into genetic counseling and accurate diagnosis of thalassemia.

[Genetic and clinical study of three Chinese pedigrees with Fabry disease].

OBJECTIVE: Fabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance. The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease. METHODS: All exons and flanking sequences of GLA gene were amplified with PCR. Potential mutations were detected with bidirectional DNA sequencing. Correlation between particular mutations and clinic features were analyzed. RESULTS: A unreported missense mutation, c.797A>C (D266A) in GLA exon 5 was identified in pedigree 1. Also in exon 5, a missense mutation c.644A>G (N215S) was found in pedigree 2. In pedigree 3, a nonsense mutation c.355C>T (Q119X) was found in exon 2. The c.797A>C mutation was not detected in 200 unrelated male controls. The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency, whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy. CONCLUSION: The unreported c.797A>C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene, and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease. The c.797A>C mutation, not found in 200 unrelated male controls, may be the causative mutation in pedigree 1. The c.644A>G and c.355C>T mutations were first detected in Chinese patients. Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.