Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians.

Area of Science:

• Genetics
• Immunology
• Endocrinology

Background:

• Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) is a rare autosomal recessive disorder.
• Mutations in the autoimmune regulator (AIRE) gene cause APECED.
• Genetic data on AIRE mutations in the Indian population is lacking.

Purpose of the Study:

• To investigate AIRE gene mutations in Indian patients with APECED.
• To identify novel mutations and characterize known mutations in this cohort.
• To understand the genetic basis of APECED in India.

Main Methods:

• Cross-sectional study of nine patients from eight families across four Indian hospitals.
• Direct sequencing of the AIRE gene in patients.
• Screening for novel mutations in 150 controls using allele-specific PCR.

Main Results:

• All patients carried homozygous AIRE mutations.
• Two novel mutations, p.V80G and p.C302X, were identified in unrelated patients.
• Previously reported Caucasian mutations, including a 13 base pair deletion (p.C322fsX372), Finn-major (p.R257X), and p.R139X, were also detected.

Conclusions:

• This is the first series of APECED cases in Indians, revealing both known and unique AIRE mutations.
• The p.V80G mutation may be an ancestral mutation within an in-bred community.
• The findings expand the spectrum of AIRE mutations associated with APECED globally.