Translating Molecular Technologies into Routine Newborn Screening Practice.

Sarah M Furnier,Maureen S Durkin,Mei W Baker

doi:10.3390/ijns6040080

Abstract

As biotechnologies advance and better treatment regimens emerge, there is a trend toward applying more advanced technologies and adding more conditions to the newborn screening (NBS) panel. In the current Recommended Uniform Screening Panel (RUSP), all conditions but one, congenital hypothyroidism, have well-defined genes and inheritance patterns, so it is beneficial to incorporate molecular testing in NBS when it is necessary and appropriate. Indeed, the applications of molecular technologies have taken NBS to previously uncharted territory. In this paper, based on our own program experience and what has been reported in the literature, we describe current practices regarding the applications of molecular technologies in routine NBS practice in the era of genomic and precision medicine.

Highlights

The goal of newborn screening (NBS) is to identify presymptomatic newborns with serious or fatal disorders that can be successfully treated, thereby achieving a significant reduction in morbidity and mortality
Strand and colleagues reported a two-tier approach in a pilot NBS for Severe Combined Immunodeficiency (SCID): the first tier consists of real-time polymerase chain reaction (PCR) for T-cell receptor excision circles (TRECs) and the second-tier next generation sequencing (NGS) of a targeted panel of primary immunodeficiencies (PIDs)-associated genes with results confirmed by Sanger sequencing [27]
We have described current applications of molecular technologies in routine NBS practice with the intention of illustrating their uses and assay principles

Summary

Introduction

The goal of newborn screening (NBS) is to identify presymptomatic newborns with serious or fatal disorders that can be successfully treated, thereby achieving a significant reduction in morbidity and mortality. In addition to an end-point-PCR TREC analysis (EnLite Neonatal TREC Kit, Perkin Elmer, Turku, Finland), Al-Mousa and colleagues performed targeted NGS using a panel of genes known to be associated with primary immunodeficiencies (PIDs), later confirmed through Sanger sequencing They used a copy number-based assay (RT-qPCR and single nucleotide polymorphism microarrays) to detect the chromosome 22q11.2 deletion, a non-SCID PID [16]. Strand and colleagues reported a two-tier approach in a pilot NBS for SCID: the first tier consists of real-time PCR for TREC and the second-tier NGS of a targeted panel of PID-associated genes with results confirmed by Sanger sequencing [27] This combination method allows the addition of relevant gene variant information to infants identified by TREC assays as at high risk for SCID as a part of the routine NBS process which has been demonstrated by the above cited three reports. Kay and colleagues acknowledged the first year of the New York state SMA NBS resulted in a much lower SMA birth incidence rate than ones reported in the literature and offered some potential explanations [35]

Screening Method

Targeted Gene Variant Panel as Second-Tier Testing

Findings

Discussion