Genomic modifiers of PHTS

Introduction

Different individuals with the same PTEN variant, even within the same family, can develop very different combinations of symptoms, with some being affected from early childhood and others only later in life. This suggests that it is not just the alteration in the PTEN gene that determines how PHTS develops in an individual and makes it difficult for doctors and people with PHTS to know what symptoms they are likely to develop.

The term ‘genome’ is used to describe the entire genetic material of an individual. Made of DNA, the genome consists of over 30,000 different genes. In between these genes is a large amount of less characterised, silent DNA, a bit like the so-called “dark matter” in the genomic universe.

An earlier PTEN Research funded project by Professor Eng’s group suggested that alterations in the silent DNA of the genome may play a role, alongside the PTEN gene variants, in determining which, how and when different PHTS symptoms may develop in an individual. 

Project goals

This  project aimed to identify specific DNA alterations that may be associated with the development of more common symptoms, such as cancer, developmental delay, and autism in PHTS.

Project overview

Professor Eng’s group has already established a large group of people with PHTS through a network of expert centres in the USA who help researchers studying PHTS and the PTEN gene. From these, approximately 600 individuals have volunteered to have their whole genome sequenced – including both their genes and the silent DNA in between. By using sophisticated analytical techniques, the researchers then hunted through the genetic sequences of these people, to see if there were certain alterations in the genome that appeared to be associated with the development of particular PHTS symptoms (such as cancer, developmental delay, autism) or combinations of symptoms.