A novel pathogenic mutation on Interleukin-7 receptor leading to severe combined immunodeficiency identified with newborn screening and whole exome sequencing

Publication date: Available online 2 March 2018Source: Journal of Microbiology, Immunology and InfectionAuthor(s): Cheng-Yu Liao, Hui-Wen Yu, Chao-Neng Cheng, Jiann-Shiuh Chen, Ching-Wei Lin, Peng-Chieh Chen, Chi-Chang ShiehAbstractBackgroundPatients with severe combined immunodeficiency (SCID), which is caused by genetic defects in immune-related genes involved in the development or activation of the adaptive immune system, often died in infancy due to severe infections before definite molecular diagnosis could be made. Although recent improvement in early diagnosis has been achieved by newborn screening, the genetic basis of many of the patients is still unknown.MethodsHere we performed whole exome sequencing (WES) to investigate the underlying genetic causes of SCID in a proband identified with newborn screening. Inheritance of the mutation was confirmed with targeted sequencing of the parents. Homozygosity mapping from the WES was used to investigate the consanguinity of the parents. Immunoblotting was used to confirm the loss of expression of the mutant protein.ResultsA novel homozygous frameshift mutation of IL7R was identified through WES. Both parents are carriers for this 1-bp deletion. HLA typing and exome-wide homozygous stretch mapping suggested that the parents are consanguineous. Immunoblotting showed no expression of IL7Rα isoform in the whole blood sample of the proband. The proband received peripheral blood stem cell transplantation and her general condition...
Source: Journal of Microbiology, Immunology and Infection - Category: Microbiology Source Type: research