Analysis of genetic mutations and pathogenesis for two children with Omenn syndrome / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the clinical characteristics and genetic mutations in two children with Omenn syndromes.</p><p><b>METHODS</b>Peripheral venous blood samples were collected from 2 children suspected with severe combined immunodeficiency (SCID) and their family members. The samples were subjected to RAG1 and RAG2 gene sequencing and TCR Vβ subclone analysis.</p><p><b>RESULTS</b>Both patients had recurrent infections, erythroderma rashes and alopecia baldness. One patient has fit with immunophenotype T-B-NK+, while another was consistent with typical Omenn syndrome combined with T+B-NK+ immunophenotype, IgE and eosinophil increase. Both children have carried compound heterozygous mutations of the RAG1 gene. The first patient carried c.1328 G>A (p.R443K) and c.2486-2490delGGAAA (p.R829fsX869) mutations, both were of de novel type. The second patient has carried c.1209C>T (p.R403W) and c.2892delT (p.ASN964LYSfs*14), with c.2892delT (p.ASN964LYSfs*14) being a de novel mutation. The parents of both patients were heterozygous carriers. The same mutations were not found in 100 healthy children. Both patients' 24 TCR Vβ subfamilies have presented monoclonal or oligoclonal peaks, with TCR Vβ polymorphism being severely disrupted.</p><p><b>CONCLUSION</b>Three novel mutations have been identified in two children with Omenn syndrome, which featured early onset and rapid progression. Early recognition of the disease and prompt treatment may reduce the mortality.</p>