Exome sequencing and rare variant analysis reveals multiple filaggrin mutations in Bangladeshi families with atopic eczema and additional risk genes

Atopic eczema (AE) is a heterogeneous chronic inflammatory skin condition that affects approximately 15-20% of children worldwide (Nutten, 2015). The prevalence varies widely among different countries, between rural and urban areas within a single country and particular Asian skin types are more sensitive to urban environments (Krutmann et al., 2014, Ben-Gashir et al., 2004, Nutten, 2015, Odhiambo et al., 2009). In this study, we analyzed the genetic architecture of AE patients from the South Asian Bangladeshi community in East London (UK) using Whole Exome Sequencing (WES) combined with rare variant enrichment analysis. A total of 70 Bangladeshi Sylheti families each with at least two affected siblings presenting with severe AE (determined by National Institute for Health and Care Excellence (NICE) guidelines) were recruited via the pediatric dermatology clinic at the Royal London Hospital, London (UK). The majority of the affected individuals were born in the UK and also presented with very high IgE levels and other atopic phenotypes, such as food allergy, asthma and hay fever.Genomic DNA was extracted from EDTA-peripheral blood samples from family members after written informed consent and in adherence with the Declaration of Helsinki Principles and approval from the East London and City Health Authority. WES was performed in 43 probands of 42 Bangladeshi families and an enrichment analysis was performed towards identifying possible AE associated rare coding gene variants. Exome capture and enrichment was performed using various versions of the Agilent capture platform. The subsequent DNA library was …