High throughput screening identifies the genetic cause underlying a rare disease in a large nationwide cohort

A collaborative study between ICH and the Turkish Pediatric Endocrinology Society has used high throughput DNA analysis to identify the genetic cause of primary adrenal insufficiency in more than 80% of affected children.

Primary adrenal insufficiency (PAI) is a rare condition that can be difficult to diagnose and is life-threatening if not treated with steroid replacement. Several genetic causes of PAI have been found in recent years but it can be difficult to know which genes to look at first as there is often great overlap in clinical and biochemical features.

This collaborative study was undertaken between Professor John Achermann’s group at ICH, Dr Tulay Guran and 19 paediatric endocrinology centres in Turkey covering approximately 15 million children. A total of 95 patients were identified with rare forms of PAI where the cause was not known. A high-throughput Haloplex DNA capture approach was developed by Dr Federica Buonocore to analyse many genes simultaneously. A specific genetic diagnosis was reached in 81% (77/95) of children.

This study – published in the Journal of Clinical Endocrinology and Metabolism – has translational impact for counselling families, diagnosing and treating affected children before symptoms occur, predicting potential associated features and for targeting genetic analysis where local founder effects are known. Professor John Achermann is a Wellcome Trust Senior Research Fellow in Clinical Science.