Exome Sequencing in Endocrine disorders Version 1.0,15.08.2015
Research type
Research Study
Full title
Whole Exome Sequencing in Rare Endocrine disorders
IRAS ID
179435
Contact name
Senthil Senniappan
Contact email
Sponsor organisation
Clinical Research Business Unit,Alder Hey Children's Hospital NHS Trust
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Molecular diagnosis is important in the management of various paediatric endocrine disorders including disorders of growth,metabolism, bone, hypoglycaemia (low blood sugar) and sexual development. Congenital Hyperinsulinism (CHI) is the most common cause of persistent and recurrent hypoglycaemia in infancy. It is the result of unregulated insulin secretion from the pancreatic β-cells leading to severe hypoglycaemia. In nearly 50% of these patients, specific genetic determinants are not known. Short stature is a common presentation to the paediatric endocrinology clinics. However, no genetic cause is identified in a large proportion of patients who are classified as having idiopathic short stature. It is estimated that the underlying genetic cause for short stature remains unknown in approximately 80% of patients. Similarly, specific genetic determinants are not known in a significant proportion of rare endocrine conditions including hypopituitarism, DSD (Disorders of Sexual Development), hypogonadism(lack or delay in puberty) and disorders of bone health. The large number of gene defects associated with the various endocrine disorders renders gene-by-gene testing increasingly expensive and unattractive. The large number of potentially relevant genes makes it challenging for hospital molecular diagnostic laboratories to offer gene-based testing to all candidates. It may be now possible to identify likely genetic causes by implementing genomic investigative techniques like whole exome sequencing (WES) in many of these children who have unknown reasons for their hypoglycaemia, poor linear growth, and various other rare endocrine problems as described before. WES in this group of patients will help to understand and identify the potential causative mutations in genes which can be very important for clinicians to manage the patients more effectively and to counsel parents on the prognosis and disease recurrence. This will help the clinicians to provide optimal treatment.Identification of novel genetic etiology has the potential to identify novel therapeutic strategies for these patients.
REC name
North West - Liverpool Central Research Ethics Committee
REC reference
15/NW/0758
Date of REC Opinion
29 Oct 2015
REC opinion
Further Information Favourable Opinion