Table 2.
New severe PIDs, debut 3–6 months, not picked up on newborn screening since born outside pilot test region.
| Patient ID | TRECs and PIDv2 panel testing on the original DBS and the new sample | |||||
|---|---|---|---|---|---|---|
| PID_1 | PID_2 | PID_3 | PID_4 | PID_5 | PID_6 | |
| Year | 2016 | 2016 | 2017 | 2017 | 2017 | 2017 |
| Symptoms at time of diagnosis | SGA, microcephaly, transient lymphopenia, persistent neutropenia and low number of platelets | SGA, microcephaly, failure to thrive, pigment patches skin | Heart defect, choanal atresia, coloboma, infections | Heart defect, prematurity, Downs syndrome | Heart defect, dysmorphic features | Infections, failure to thrive |
| Gender | Female | Male | Male | Male | Male | Female |
| GA w | 35 | 36 | 36 | 33 | 34 | 40 |
| BW g | 1,920 | 1,534 | 2,445 | 1,570 | 3,430 | |
| TRECs/μl at birth |
4.69 | 1.9 | 0 | 9.7 | 15.7 | 71.8 |
| Repeated TRECs/ul (age) | 23.8 (3 months) 0 (12 months) |
0 (4 months) | 0 (1.5 months) | 0 (2 months) | NA | 12.2 (6.8 months) |
| Gene | unknown | unknown | CHD7 | Trisomy 21 | TBX1 | IKZF1 |
| SNV/CNV | NA | NA | c.[5833C>T];[=] | 47, XY, +21 | 22q11.21 del | c.[476A < G];[=] |
| Protein | NA | NA | p.Arg1945* | NA | NA | p.Asn159Ser |
| Refseq | NA | NA | NM_017780.3 | NA | NA | NM_006060.4 |
| Methods | PIDv2 gene panel, WES/WGS trio | PIDv2 gene panel, WES/WGS trio | Sanger | Trisomy test | MLPA, Trisomy test |
PIDv2 gene panel |
| Treatment and outcome | Deceased at 1 ½ years of age | HSCT, Successful | Prophylactic antibiotics, antifungal, antiviral and ScIg therapy | Heart surgery. Lymphopenia 1.9 × 109/L at 1 years of age, but no recurrent infections |
Prophylactic antibiotics | HSCT, Successful |
aCGH, array comparative genomic hybridization chromosomal/chromosomal microarray; BW, Birth weight; CNV, Copy number variation; g, gram; GA, Gestational age; HGNC, The HUGO Gene Nomenclature Committee; HSCT, Hematopoietic Stem Cell Transplantation; MLPA, multiplex ligation-dependent probe amplification; NA, Not applicable; NBS, Newborn screening; ND, Not detected; PIDv2, Primary immunodeficiency research panel version 2; PIDs, Primary immunodeficiencies; RefSeq, The National Center for Biotechnology Information Reference Database; SCID, Severe combined immunodeficiency; ScIg, Subcutaneous Immunoglobulin; SGA, Small for gestational age; SNV, Single nucleotide variant; TREC, T-cell receptor excision circles; Trio-test; testing the child and both parents in comparison; WES, whole exome sequencing; WGS, whole genome sequencing w, week.
Resources: Gene names according to HGNC, https://www.genenames.org/.
Gene variant nomenclature according to the HGVS recommendations, http://www.HGVS.org/varnomen.