Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant with Primary Immunodeficiency

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Primary immunodeficiencies (PIDs) are rare inherited disorders affecting immune system function.
• Clinical and immunological signs can suggest specific PIDs, necessitating genetic investigation.

Purpose of the Study:

• To investigate a male infant with suspected PID using advanced genetic sequencing.
• To identify the causative genetic mutation for accurate diagnosis and family screening.

Main Methods:

• Whole-exome sequencing was performed on the infant and his parents.
• Analysis focused on identifying novel genetic variants in PID-associated genes.

Main Results:

• A novel cytosine to adenine substitution at nucleotide position 252 in the IL2RG gene was identified.
• This mutation (p.Asn84Lys) results in a pathogenic amino acid change in the IL2RG protein.
• The infant's mother was identified as a carrier, consistent with X-linked inheritance.

Conclusions:

• The identified mutation confirms a diagnosis of X-linked severe combined immunodeficiency in the infant.
• This is the first reported IL2RG mutation of this type in an Indian family.
• Next-generation sequencing is a powerful tool for PID diagnosis, prenatal screening, and carrier detection, paving the way for individualized medicine.