Potential protein–phenotype correlation in three lipopolysaccharideresponsive beige-like anchor protein-deficient patients  

作　　者：Wen-Juan Tang Wen-Hui Hu Ying Huang Bing-Bing Wu Xiao-Min Peng Xiao-Wen Zhai Xiao-Wen Qian Zi-Qing Ye Hai-Jiao Xia Jie Wu Jie-Ru Shi 

机构地区：[1]Department of Gastroenterology,Pediatric Inflammatory Bowel Disease Research Center,Children’s Hospital of Fudan University,National Children's Medical Center,Shanghai 201102,China [2]The Molecular Genetic Diagnosis Center,Children's Hospital of Fudan University,Shanghai 201102,China [3]Department of Hematology Oncology,Children's Hospital of Fudan university,National Children's Medical Center,Shanghai 201102,China

出　　处：《World Journal of Clinical Cases》2021年第21期5873-5888,共16页世界临床病例杂志

摘　　要：BACKGROUND Patients with lipopolysaccharide(LPS)-responsive beige-like anchor protein(LRBA)deficiency have a variety of clinical symptoms,but there is no apparent genotype–phenotype correlation,and patients carrying the same mutations may have different phenotypes.Therefore,it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation(HSCT)for LRBA-deficient patients.We hypothesized that there may be a protein–phenotype correlation to indicate HSCT for LRBA-deficient patients.AIM To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes.METHODS Clinical data of three Chinese LRBA-deficient patients were collected,and protein levels were detected by Western blot analysis.In addition,LRBA mutation information of another 83 previously reported patients was summarized.RESULTS All the major clinical findings indicated enteropathy,but patients 1 and 3 presented with more severe symptoms than patient 2.Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2.Compound heterozygous mutations in LRBA were found in patient 1,and homozygous mutations in LRBA were found in patient 2 and patient 3.Only patient 2 responded well to traditional immunosuppressive treatment.Residual expression of the LRBA protein in patients 1 and 3 was very low,but in patient 2,a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control.After HSCT,patient 1 had increased LRBA protein expression.We summarized the genetic information of 86 patients,and the mutations in patients 1 and 3 were novel mutations.CONCLUSION We described three Chinese LRBA-deficient patients,two of whom carried novel mutations.These patients had no genotype-phenotype correlations,but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.

关 键 词：LPS-responsive beige-like anchor protein deficiency Chinese Common variable immunodeficiency Gene mutation Chronic diarrhea 

分 类 号：R725.9[医药卫生—儿科]