Multigenerational evidence of X-linked adrenal hypoplasia congenita due to a novel NR0B1 frameshift

Pathogenic NR0B1 variants, encoding DAX-1, are a major cause of X-linked adrenal hypoplasia congenita (AHC), yet genotype–phenotype variability persists. In a Chinese four-generation pedigree, two affected males carried a novel NR0B1 frameshift, c.573_576dup4 (p.T193Gfs*13). Segregation showed wild-type fathers and heterozygous carrier mothers, and unaffected male relatives lacked the variant. The duplication shifts the reading frame from residue 193 and introduces a premature stop at residue 205, truncating DAX-1. Pedigree analysis supports NR0B1 c.573_576dup4 (p.T193Gfs*13) as a novel AHC-causing variant. This maternally inherited frameshift underlies AHC in this family, expanding the NR0B1 mutational spectrum and underscoring genetic testing.