Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain

AbstractInterleukin 2 receptor alpha chain (IL-2R α or CD25) deficiency (OMIM #606367) is an immune dysregulation disorder segregating in autosomal recessive form. The disease is caused by biallelic variants in theIL-2Rα gene encoding IL-2Rα also known as CD25 protein. IL-2Rα combines with γ and β chains of interleukin 2 receptor to form a functional interleukin 2 receptor (IL-2R). In the present study, we identified a Pakistani family presenting a unique presentation of IL-2Rα deficiency. Clinical whole exo me sequencing revealed a novel splice donor site variant (NM_001378789.1 (NP_001365718); c.64 + 1G >  A) in theIL-2R α gene. American College of Medical Genetics (ACMG) guidelines interpreted the identified variant as likely pathogenic. TheIL-2R α gene mutation usually presents with autoimmunity and immunodeficiency but in our patient, it presents with congenital diarrhea, metabolic crisis, and strong family history of death in infancy due to the similar complications. Her congenital diarrhea is attributed to autoimmunity in the form of autoimmune enteropathy and eczema. The laboratory findings revealed severe metabolic acidosis hypokalemia and elevated lactate and ammonia levels. This is a new presentation ofIL-2R α gene mutation. The present study highlights the importance of clinical whole exome sequencing in the correct diagnosis of congenital disorders. The study will also help clinical geneticists for genetic counseling and prevention of the dis...

Source: Immunogenetics - October 4, 2022 Category: Genetics & Stem Cells Source Type: research