Molecular assessment of thymic capacities in patients with Schimke immuno-osseous dysplasia.
Schimke immuno-osseous dysplasia (SIOD) is caused by SMARCAL1 deficiency and characterized by defective T-cell immunity. The immunodeficiency and the role of thymic function in SIOD patients are not clearly understood. We performed thymic evaluations by assessing T-cell receptor (TCR) diversity, rearrangement, and excision circles in family members with different disease severity carrying the same bi-allelic mutation and in a heterozygous carrier. The expression of SMARCAL1 mRNA in a normal thymic sample was measured using real-time quantitative polymerase chain reaction. Thymus functions were significantly reduced in SIOD patients, and these findings were highly correlated with the clinical phenotype. Quantification of SMARCAL1 mRNA transcript was 3.86-fold higher than normal values for adult kidneys. Genotype alone apparently does not define phenotype, and analysis of TCR diversity, rearrangement, and thymus output can quantify the extent of T-cell immunodeficiency. High thymic expression of SMARCAL1 mRNA raises the possibility of its importance in thymus maintenance and function.
Lev
Atar
A
Cancer Research Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv, Israel.
Amariglio
Ninette
N
Levy
Yael
Y
Spirer
Zvi
Z
Anikster
Yair
Y
Rechavi
Gideon
G
Dekel
Benjamin
B
Somech
Raz
R
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001848:Bone Diseases, Developmental / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002675:Child, Preschool; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D007136:Immunoglobulins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C412482:SMARCAL1 protein, human; D004265:DNA Helicases