Rare Diseases Symptoms Automatic Extraction

Novel point mutation of the α2-globin gene (HBA2) and a rare 2.4 kb deletion of the α1-globin gene (HBA1), identified in two chinese patients with Hb H disease.


Two Chinese patients with mild and moderate Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2) in addition to the - -(SEA) deletion. One patient was a 41-year old man with mild anemia (Hb 11.3g/dL). Multiplex ligation-dependent probe amplification (MLPA) revealed a rare 2392bp deletion involving the entire HBA1 gene. Mapping by gap-polymerase chain reaction (gap-PCR) defined the exact breakpoints of this deletion (HBA1: g36859_39252del2392) and confirmed its identity with a recently reported HBA1 deletion found in a Southern Chinese. The other patient was a 53-year old man with moderate anemia (Hb 9.5g/dL). Automated direct nucleotide (nt) sequencing identified a novel single nt deletion at codon 40 (HBA2: c.123delG). This leads to a frameshift that modifies the C-terminal sequence to (40)Lys-Pro-Thr-Ser-Arg-Thr-Ser-Thr(47)COOH and the introduction of a stop codon TGA 23 nts downstream. These two cases demonstrate the power of MLPA and direct nt sequencing to detect and characterize rare and novel mutations. They also highlight the differential effect of HBA1 and HBA2 gene mutations on an α-thalassemia (α-thal) phenotype due to their different transcriptional activity.