Genotype and Phenotype of 21-Hydroxylase Deficiency: A Single Center Experience from Western India

To describe the genotype-phenotype characteristics of patients with 21-hydroxylase deficiency from Western India and ascertain the prevalence of various phenotypes of 21-hydroxylase deficiency.

Patients with 21-hydroxylase deficiency, diagnosed clinically and biochemically, were prospectively enrolled and classified into salt wasting (SW), simple virilizing (SV), and non-classic (NC) phenotypes and were subjected to genetic testing of CYP21A2 by targeted sequencing and multiplex ligation-dependent probe amplification (MLPA).

Eighty (64; 46, XX) probands with 21-hydroxylase deficiency were analyzed. 41 had SW, 34 had SV, and 5 had NC phenotype. Disease-causing mutations were identified in 158/160 alleles. The common mutations were Deletions/Large Gene Conversions (Del/LGC, 25.6%), p.293–13A/C>G (22.5%), and p.Ile173Asn (18.75%). Exon 6 cluster mutations (Ile236Asn, Val237Glu, Met238Lys) and p.Val282Leu were absent. c.−113G>A+p.Pro31Leu (6.87%) and p.Phe405Ser (2.5%) were rare recurrent mutations with a possible founder effect. Two novel variants (Exon 1, p.Leu49Arg, Exon 8, p.Leu362Ter) were identified and were estimated to have low enzyme activity (<2%).

Del/LGC were the most common mutations identified. c.−113G>A+p.Pro31Leu and p.Phe405Ser were recurrent variants with possible founder effect. This study also reiterates the low prevalence of NC phenotype in Indian cohorts.