Clinical and genetic landscape of SCID in Yunnan, China: identification of two novel RAG2 variants

Severe combined immune deficiency (SCID) is a rare inherited defect of lymphocytes causing life-threatening opportunistic infections in early infancy. Data on SCID from China are limited. This study explores the clinical, immunologic, and genetic features of a SCID cohort from Yunnan Province in China and reports novel variants. We collated clinical, laboratory, and molecular details from patients with a clinical profile suggestive of SCID. Trio-based whole-exome sequencing was performed to identify genetic variants. For the 9 previously reported variants identified in our cohort, we systematically reviewed the literature for additional cases carrying the same variants and compared clinical and immunologic features. Eleven infant patients (8 males and 3 females) were included. Molecular diagnoses were obtained in 10 patients, as follows: IL2RG (3), RAG2 (3), LIG4 (2), DCLRE1C (1), and CD3D (1). Nine patients presented with classic SCID features within the first 3 months of life. Eleven variants were identified: 2 novel RAG2 variants (p.L469P and p.Q492R) and 9 variants previously reported in SCID-associated genes. One patient with the p.Q492R variant exhibited a relatively milder clinical course. An extremely rare case of Omenn syndrome due to IL2RG deficiency was also observed. Ten of 11 patients died within 6 months of age. The literature review identified 94 additional cases carrying these same variants; clinical presentations were generally consistent with our patients, although some variability was observed. We characterized the clinical and genetic profiles of 11 SCID patients from Yunnan, China, identifying two novel RAG2 variants. While these findings expand the mutational spectrum in understudied populations, the high mortality and diagnostic delays observed here underscore the critical need for universal newborn screening in China. Further functional studies are required to confirm the impact of the identified variants.