Identification of a Novel Variant c.163delG in HBB Gene Resulting in a Beta Null Phenotype in a Proband with Thalassemia Intermedia.

A 21-year-old patient presented with a previous medical history of pallor, mild icterus, increased fatigue, low hemoglobin, and abnormal hemoglobin variant analysis with more than 70 transfusions. He was referred for genetic analysis to identify the pathogenic variations in the ß-globin gene. Sanger's sequencing of the proband and his family revealed the presence of a novel frame shift variant HBB:c.163delG in a compound heterozygous state with hemoglobin E (HbE) (HBB:c.79G > A) variant. The father and the sibling of the patient were found to be normal for the HBB gene. Mother was found to be heterozygous for HbE (HBB:c.79G > A) variant. In silico analysis by Mutalyzer predicted that c.163delG variant generated a premature stop codon after seven codons, leading to a truncated protein. FoldX protein stability analysis showed a positive ΔΔG value of 45.27 kcal/mol suggesting a decrease in protein stability. HBB:c.79G > A is a known variant coding for HbE variant, which results in the reduced synthesis of ß-globin chain and shows mild thalassemia. Combined effect of HBB:c.163delG and HBB:c.79G > A variants in the proband might have led to the reduced synthesis of ß-globin chains resulting in a thalassemia intermedia type of clinical manifestation.

The Phenomenon Of Dissociation, Depression And Borderline Personality In A Young Woman

Early life adversities like parental loss during childhood, physical abuse, sexual abuse and emotional harassment may have deleterious consequences in an individual’s life, which can manifest under the form of various externalizing or internalizing behaviors. This case study aimed to highlight the impact of unusual early life adversities in a young woman’s mental health and related management issues. Methods: We reported a case of a young lady presenting with anxiety, low mood, disturbed sleep and appetite for more than six months. She also had episodes of dissociative stupor following any stressful event for approximately 13 years. She was hospitalized, evaluated clinically as well as by psychometric assessment. Relevant pharmacological and psychological interventions were performed. Results: She was diagnosed with Major depressive disorder with dissociative disorder and borderline personality disorder. The patient had multiple stressors during childhood like - loss of parents, emotional & physical abuse, which had an impact on her mental wellbeing. Conclusion: Early life adversities are detrimental to the mental health of an individual. The clinical outcome depended upon on the nature of trauma to the mental well-being, mode of intervention done and available psychosocial supports. ASEAN Journal of Psychiatry, Vol. 17 (2): July – December 2016: XX XX.