Genetic Profiling of Children with Advanced Cholestatic Liver Disease

ABSTRACT

Advanced cholestatic liver disease is a leading referral to pediatric liver transplant centers. Recent advances in the genetic classification of this group of disorders promise a highly personalized management although the genetic heterogeneity also poses a diagnostic challenge. Using a next-generation sequencing-based multi-gene panel, we performed retrospective analysis of 98 pediatric patients who presented with advanced cholestatic liver disease. A likely causal mutation was identified in the majority (61%), spanning many genes including ones that have only rarely been reported to cause cholestatic liver disease e.g. TJP2 and VIPAS39. We find no evidence to support mono-allelic phenotypic expression in the carrier parents despite the severe nature of the respective mutations, and no evidence of oligogenicity. The high carrier frequency of the founder mutations identified in our cohort (1 in 87) suggests a minimum incidence of 1:7,246, an alarmingly high disease burden that calls for the primary prevention through carrier screening.

from Genetics via xlomafota13 on Inoreader http://ift.tt/2iP5OhM
via IFTTT