Unusual presentation of DCLRE1C gene-related SCID: A case report of challenging molecular diagnosis

Background. Severe combined immunodeficiency (SCID) is a critical genetic condition that hampers immune system development, often fatal if not diagnosed and treated promptly. Infants with SCID require urgent hematopoietic stem cell transplantation, with the best outcomes seen when diagnosis and treatment occur before 3.5 months of age.

This report outlines the case of a 1.5-year-old boy with SCID who exhibited unusual symptoms after receiving the BCG vaccine at 2 months. Despite an atypical immunological profile with the presence of CD3+ and CD4+ cells, the absence of CD8+ cells hinted at a potential primary immunodeficiency.

Methods. Next-generation sequencing of Primary Immunodeficiency gene panel revealed a deletion of DCLRE1C gene exons 1-3 was identified. The deletion has 0.2 reads ratio, which is borderline value between homozygous and heterozygous deletion. However, QC revealed ~15% cell contamination (with female sample). The contamination was identified also from freshly extracted blood sample on chromosomal microarray and confirmed to be of maternal origin by QF-PCR. The deletion was confirmed to be homozygous in child, confirming the SCID diagnosis. Karyotype culture failed to grow, precluding karyotyping - a phenomenon often observed in ‘null’ variants of DCLRE1C gene.

Results: These findings confirmed the diagnosis of DCLRE1C gene-related SCID. The homozygous deletion could be missed or misinterpreted as heterozygous as the sample was “contaminated” with maternal cell line.

Conclusion: This case underscores critical importance of newborn screening for such conditions, a practice initiated in Latvia as of April 1, 2023. Understanding SCID biology and genetics is important for correct diagnosis.