基因突变致LIG4综合征临床及基因特征OA北大核心CSTPCD

Objective To explore the clinical and genetic characteristics of LIG4 syndrome.Methods We retrospectively analyzed the clinical data of 3 patients with LIG4 syndrome who were admitted to ShangHai Children'S Hospital from Jun 2014 to Aug 2018,and reviewed related articles.Results All 3 cases were female,presented with recurrent chronic diarrhea or recurrent respiratory infections.The clinical manifestations were microcephaly,a special"bird-head-like"face,growth retardation,and repeated infections.The blood routine showed that the lymphocyte count was significantly reduced,the immune function showed that the counts of T and B lymphocytes were decreased,and immunodeficiency disease was considered clinically.The gene detection revealed that P1 had homozygous mutation of LIG4 gene,c.833G＞T(p.R278L),with severe clinical phenotype;P2 had LIG4 gene complex heterozygous mutations,c.883G＞T(p.R278L)and c.1144-1145delCT(p.L382EfsX5);P3 had LIG4 gene complex heterozygous mutations,c.28-29delGT(p.vall0fs)and c.1341G＞T(p.Trp447cys),where the frameshift gene mutation site,c.28-29delGT(p.vall0fs),had not been reported.P1 died of severe infection and multiple organ dysfunction syndrome.P2 had preventive anti-infection treatment and received regular human immunoglobulin infusion,who still had recurrent infection and lost follow-up.P3 underwent peripheral blood hematopoietic stem cell transplantation,and established normal immune function.She did not have recurrent infection during 2-year follow-up period.A total of 46 cases of LIG4 syndrome had been published worldwide,including 13 cases and 1 family report of LIG4 syndrome in China.Conclusion Immunodeficiency diseases should be considered in the patients with chronic multiple infections accompanied by T and B lymphocytes decrease,growth retardation,and microcephaly.Gene testing helps confirm the diagnosis and prenatal screening.Hematopoietic stem cell transplantation is effective for immune reconstitution.