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

Authors

• Manjiri Karlekar
• Rohit Barnabas
• Vijaya Sarathi
• Anurag Lila
• Sneha Arya
• Samiksha Hegishte
• Vishwambhar V Bhandare
• Saba Samad Memon
• Virendra Patil
• Tushar Bandgar
• Ambarish Kunwar
• Nalini Shah

Language

English

Publication Date

10-15-2024

Journal

Indian Pediatrics

PMID

39051316

Abstract

Objective: 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.

Methods: 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).

Results: 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%).

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

Keywords

Humans, Adrenal Hyperplasia, Congenital, India, Female, Male, Phenotype, Steroid 21-Hydroxylase, Infant, Genotype, Infant, Newborn, Mutation, Child, Preschool, Child, Prospective Studies

Published Open-Access

yes

Recommended Citation

Karlekar, Manjiri; Barnabas, Rohit; Sarathi, Vijaya; et al., "Genotype and Phenotype of 21-Hydroxylase Deficiency: A Single Center Experience from Western India" (2024). Faculty, Staff and Student Publications. 4416.
https://digitalcommons.library.tmc.edu/uthmed_docs/4416