TY - JOUR

T1 - Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain

AU - Waheed, Nadia

AU - Naseer, Maryam

AU - Haider, Nighat

AU - Suleman, Sufyan

AU - Ullah, Asmat

N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2023

Y1 - 2023

N2 - Interleukin 2 receptor alpha chain (IL-2Rα or CD25) deficiency (OMIM #606367) is an immune dysregulation disorder segregating in autosomal recessive form. The disease is caused by biallelic variants in the IL-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 exome sequencing revealed a novel splice donor site variant (NM_001378789.1 (NP_001365718); c.64 + 1G > A) in the IL-2Rα gene. American College of Medical Genetics (ACMG) guidelines interpreted the identified variant as likely pathogenic. The IL-2Rα 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 of IL-2Rα 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 disease in the affected family.

AB - Interleukin 2 receptor alpha chain (IL-2Rα or CD25) deficiency (OMIM #606367) is an immune dysregulation disorder segregating in autosomal recessive form. The disease is caused by biallelic variants in the IL-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 exome sequencing revealed a novel splice donor site variant (NM_001378789.1 (NP_001365718); c.64 + 1G > A) in the IL-2Rα gene. American College of Medical Genetics (ACMG) guidelines interpreted the identified variant as likely pathogenic. The IL-2Rα 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 of IL-2Rα 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 disease in the affected family.

KW - Clinical whole exome sequencing

KW - IL-2R α deficiency

KW - Novel variant

U2 - 10.1007/s00251-022-01278-1

DO - 10.1007/s00251-022-01278-1

M3 - Journal article

C2 - 36195682

AN - SCOPUS:85139385789

VL - 75

SP - 71

EP - 79

JO - Immunogenetics

JF - Immunogenetics

SN - 0093-7711

ER -