Screening for genetic immune disorders using newborn genetic testing

AIFA Early Career and New Researcher Grant

Dr Isabelle Bosi

Garvan Institute of Medical Research, Children’s Hospital Westmead and Royal Prince Alfred Hospital, Sydney

Research Team: A/Prof Owen Siggs, A/Prof Elissa Deenick, JOnathan Nguyen (Garvan Institute of Medical Research), Prof Bruce Bennetts, Dr Enzo Ranieri, Dr Melanie Wong (Children’s Hospital Westmead) A/Prof Paul Gray (Sydney Children’s Hospital), Dr Kahn Preece (John Hunter Hospital, Newcastle), A/Prof Stephen Adelstein (Royal Prince Alfred Hospital), Dr Joanne Smart (Royal Children's Hospital, Melbourne), Dr Natasha Moseley (Perth Children’s Hospital), A/Prof Jane Peake (Queensland Children's Hospital), Dr Jovanka King (The Women’s and Children’s Hospital, Adelaide)

Primary immune deficiencies (PID), also known as Inborn errors of immunity (IEI) are a group of genetic conditions that affect the function of a person's immune system. This may cause infections and/or abnormal immune activity. Severe Combined Immunodeficiency (SCID) is a sub-group of IEI that cause abnormal development of essential immune cells. SCID is fatal without treatment and early detection improves survival.

A newborn screening test for SCID is now offered to all newborns in Australia. This involves collecting blood from a heel prick onto card and testing for normal byproducts of immune cell development (TRECs and, in some states, KRECs). The current test is very useful, but it cannot pick up all children with SCID or IEI. The test also cannot diagnose the sub-type of SCID, which is important for choosing the best treatment.

This project will investigate whether routine genetic testing (whole genome sequencing or WGS) performed on newborn screening cards can improve the diagnosis of SCID and other IEIs. WGS may be useful as an upfront test or after abnormal TREC and/or KREC levels are identified.

This study has 3 main aims. Firstly, the team will perform whole genome sequencing on the NBS cards of individuals with diagnosed IEI, to see if they can pick up their diagnosis using WGS alone. Next, they will perform WGS on the NBS cards of newborns with an abnormal TREC/KREC result. They will explore whether a fast, accurate diagnosis can be made with WGS alone. Finally, the researchers will study whether new tests can be developed that may be helpful for diagnosing IEI as a newborn.

The team hopes that this study will improve the diagnosis of IEI and allow earlier access to treatment.