Whole-exome sequencing identifies an α-globin cluster triplication resulting in increased clinical severity of β-thalassemia

Whole-exome sequencing (WES) has been increasingly useful for the diagnosis of patients with rare causes of anemia, particularly when there is an atypical clinical presentation or targeted genotyping approaches are inconclusive. Here, we describe a 20-yr-old man with a lifelong moderate-to-severe anemia with accompanying splenomegaly who lacked a definitive diagnosis. After a thorough clinical workup and targeted genetic sequencing, we identified a paternally inherited β-globin mutation (HBB:c.93-21G>A, IVS-I-110:G>A), a known cause of β-thalassemia minor. As this mutation alone was inconsistent with the severity of the anemia, we performed WES. Although we could not identify any relevant pathogenic single-nucleotide variants (SNVs) or small indels, copy-number variant (CNV) analyses revealed a likely triplication of the entire α-globin cluster, which was subsequently confirmed by multiplex ligation-dependent probe amplification. Treatment and follow-up was redefined according to the diagnosis of β-thalassemia intermedia resulting from a single β-thalassemia mutation in combination with an α-globin cluster triplication. Thus, we describe a case where the typical WES-based analysis of SNVs and small indels was unrevealing, but WES-based CNV analysis resulted in a definitive diagnosis that informed clinical decision-making. More generally, this case illustrates the value of performing CNV analysis when WES is otherwise unable to elucidate a clear genetic diagnosis

Helping Children Exposed to War and Violence: Perspectives from an International Work Group on Interventions for Youth and Families

Background: This paper outlines conclusions from a three-day workgroup hosting the eight authors as well as others with expertise in the evaluation and treatment of youth exposed to war and violence. Objective: The purpose of this meeting was to bring multiple perspectives together to identify components that comprise effective psychosocial interventions for child victims of war and community violence across cultures. The meeting also sought to identify gaps in the existing treatment approaches. Method: In the meeting, personal experiences and previous research were discussed to develop a wide-ranging intervention approach, determine a cohesive definition for indirect exposure, and identify successful methods of intervention delivery for youth exposed to acts of war and violence. Results and Conclusions: Key components of intervention for youth exposed to war/violence, important outcome measures, and cultural differences that may influence effective intervention were identified. A clearer definition of indirect exposure was also developed. Finally, a nine-phase model was developed to provide guidelines for establishing partnerships between trauma teams and other organizations or schools to implement and disseminate treatment for this population. © 2013 Springer Science+Business Media New York