Detecting 22q11.2 Deletion Syndrome in Newborns with Low T Cell Receptor Excision Circles from Severe Combined Immunodeficiency Screening

• Published in: The Journal of pediatrics Vol. 204; pp. 219 - 224.e1
• Main Authors: Liao, Hsuan-Chieh, Liao, Chien-Hui, Kao, Shu-Min, Chiang, Chuan-Chi, Chen, Yann-Jang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019
• Subjects: 22q11.2 deletion syndrome; copy number assay; DiGeorge syndrome; multiplex ligation-dependent probe amplification; newborn screening; severe combined immunodeficiency; T-cell receptor excision circle; 22q11.2 deletion syndrome; DiGeorge syndrome; T-cell receptor excision circle; severe combined immunodeficiency; SCID; multiplex ligation-dependent probe amplification; MLPA; copy number assay; 22q11.2DS; qPCR; TREC; newborn screening; PCR
• ISSN: 0022-3476; 1097-6833; 1097-6833
• DOI: 10.1016/j.jpeds.2018.08.072

Based on experiences and results from newborn screening for severe combined immunodeficiency (SCID), we evaluated the occurrence of chromosome 22q11.2 deletion syndrome (22q11.2DS) in newborns with different T cell receptor excision circles (TREC) results and established a second tier genetic test for 22q11.2DS. Recalled dried blood spots from 486 newborns with TREC results <90 copies/uL were tested from the SCID newborn screening. Quantitative real-time polymerase chain reaction assay was used to detect the copy number of TBX1 and HIRA genes by simple DNA extraction method. Multiplex ligation dependent probe amplification was used for further confirmation. Four hundred sixty-eight cases were considered negative because their haploid copy number of TBX1 and HIRA genes was >0.75. Eighteen cases with TBX1 and/or HIRA gene copy number <0.75 were suspected as positive, and 13 cases were further confirmed with 22q11.2DS. Detection rates of 22q11.2DS were 10.7% (6/56) in TREC <30 copies, 6.8% (9/132) in <50 TREC copies, 4.6% (12/260) in <70 TREC copies, and 2.7% (13/486) in <90 TREC copies. 22q11.2DS detection can be incorporated into the second-tier assay in subjects with low TREC copies in SCID screening. The dried blood spot methods were feasible for 22q11.2DS newborn screening.