Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome

Introduction and objectives Omenn syndrome (OS) is a very rare type of severe combined immunodeficiencies manifested with erythroderma, eosinophilia, hepatosplenomegaly, lymph-adenopathy, and elevated level of serum IgE. OS is inherited with an autosomal recessive mode of inheritance. Germline mutations in the human RAG1 gene cause OS. Materials and methods In this study, we investigated a 2-month-old boy with cough, mild anaemia, pneumonia, immunodeficiency, repeated infection, feeding difficulties, hepatomegaly, growth retardation, and heart failure. Parents of the proband were phenotypically normal. Results Karyotype analysis and chromosomal microarray analysis found no chromosomal structural abnormalities (46, XY) and no pathogenic copy number variations (CNVs) in the proband. Whole-exome sequencing identified a novel homozygous single nucleotide deletion (c.2662delC) in exon 2 of the RAG1 gene in the proband. Sanger sequencing confirmed that both the proband parents were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters and one elder brother of the proband and in the 100 ethnically matched normal healthy individuals. This novel homozygous deletion (c.2662delC) leads to the frameshift, which finally results in the formation of the truncated protein (p.Leu888Phefs*3) V(D)J recombination-activating protein 1 with 890 amino acids compared with the wildtype V(D)J recombination-activating protein 1 of 1043 amino acids. Hence, it is a loss-of-function variant. Conclusion Our present study expands the mutational spectrum of the RAG1 gene associated with OS. We also strongly suggested the importance of whole-exome sequencing for the genetic screening of patients with OS (AU)

Distribution of peripheral blood lymphocyte subpopulations in 654 children of preschool age / 国际儿科学杂志

Objective To investigate the distribution of peripheral blood lymphocyte subpopulations in 654 children aged 28 days to 7 years,and to provide a basis for establishing a normal reference range.Methods A total of 654 healthy Han children aged 28 days to 7 years were enrolled.The children were divided into infant group (28 days-12 months) (180 cases,27.52％),toddler group (1-3 years) (184 cases,28.13 ％),and preschooler group (3-7 years) (290 cases,44.34％).Peripheral blood samples were collected,and the percentages of lymphocyte subpopulation were detected by flow cytometry.Results There were statistically significant differences between boys and girls in CD3+ CD4 + T cells,CD3 + CD8 + T cells percentages and the CD4 +/CD8 + ratio in infant group (Z =-2.595,3.317,-3.492,all P ＜ 0.05);in CD3 +CD4 + T cells percentage in toddler group (Z =2.312,P ＜ 0.05);in CD3 + T cells,CD3 + CD4 + T cells,CD3-CD19 + B cells,CD3-CD16 + CD56 + NK cells percentages and the CD4 +/CD8 + ratio in preschool age group (Z =4.088,4.991,3.129,-6.949,2.141,all P ＜ 0.05).The comparison in all age groups showed significant differences in CD3 + T cells,CD3 + CD4 + T cells,CD3-CD19 + B cells,CD3-CD16 +CD56 + NK cells percentages and the CD4 +/CD8 + ratio in boys (x2 =6.925,51.543,39.563,87.751,30.334,all P ＜ 0.05),in CD3 + CD4 + T cells,CD3 + CD8 + T cells,CD3-CD16 + CD56 + NK cells percentages and the CD4 +/CD8 + ratio in girls (x2 =27.646,44.046,26.066,54.238,all P ＜ 0.05).The CD3 +CD4+ T cells and CD3-CD19+ B cells percentages declined with age (x2 =82.345,40.214,all P ＜0.05);The CD3+ CD8+ T cells and CD3-CD16+ CD56+ NK cells percentages increased with age (x2 =38.43,108.302,all P ＜0.05).Conclusion The peripheral blood lymphocyte subpopulation values differ by gender and age.It is necessary to establish the reference range of lymphocyte subpopulations for children in Lanzhou according to gender and age.

Distribution of peripheral blood lymphocyte subpopulations in 654 children of preschool age / 国际儿科学杂志

Objective@#To investigate the distribution of peripheral blood lymphocyte subpopulations in 654 children aged 28 days to 7 years, and to provide a basis for establishing a normal reference range.@*Methods@#A total of 654 healthy Han children aged 28 days to 7 years were enrolled.The children were divided into infant group(28 days-12 months)(180 cases, 27.52%), toddler group(1-3 years)(184 cases, 28.13%), and preschooler group(3-7 years)(290 cases, 44.34%). Peripheral blood samples were collected, and the percentages of lymphocyte subpopulation were detected by flow cytometry.@*Results@#There were statistically significant differences between boys and girls in CD3+ CD4+ T cells, CD3+ CD8+ T cells percentages and the CD4+ /CD8+ ratio in infant group(Z=-2.595, 3.317, -3.492, all P<0.05); in CD3+ CD4+ T cells percentage in toddler group(Z=2.312, P<0.05); in CD3+ T cells, CD3+ CD4+ T cells, CD3-CD19+ B cells, CD3-CD16+ CD56+ NK cells percentages and the CD4+ /CD8+ ratio in preschool age group(Z=4.088, 4.991, 3.129, -6.949, 2.141, all P<0.05). The comparison in all age groups showed significant differences in CD3+ T cells, CD3+ CD4+ T cells, CD3-CD19+ B cells, CD3-CD16+ CD56+ NK cells percentages and the CD4+ /CD8+ ratio in boys(χ2=6.925, 51.543, 39.563, 87.751, 30.334, all P<0.05), in CD3+ CD4+ T cells, CD3+ CD8+ T cells, CD3-CD16+ CD56+ NK cells percentages and the CD4+ /CD8+ ratio in girls(χ2=27.646, 44.046, 26.066, 54.238, all P<0.05). The CD3+ CD4+ T cells and CD3-CD19+ B cells percentages declined with age(χ2=82.345, 40.214, all P<0.05); The CD3+ CD8+ T cells and CD3-CD16+ CD56+ NK cells percentages increased with age(χ2=38.43, 108.302, all P<0.05).@*Conclusion@#The peripheral blood lymphocyte subpopulation values differ by gender and age.It is necessary to establish the reference range of lymphocyte subpopulations for children in Lanzhou according to gender and age.