• Users Online: 116
  • Print this page
  • Email this page
Year : 2022  |  Volume : 2  |  Issue : 1  |  Page : 47-51

Implications of CYP21A2 gene duplications in carrier screening and prenatal diagnosis of congenital adrenal hyperplasia due to 21 Hydroxylase deficiency

Molecular Genetics Laboratory, Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India

Correspondence Address:
Dr. Sudhisha Dubey
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi - 110 060
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_211_21

Rights and Permissions

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that presents as salt wasting or simple virilization (SV). It is due to biallelic mutations in the CYP21A2 gene that encodes the 21-hydroxylase enzyme. This gene is susceptible to deletions and duplications due to the presence of a homologous pseudogene and its location in the RCCX module. This complicates the interpretation of molecular analysis of the CYP21A2 gene. Clinical Description: During preconception counseling and subsequent workup of a couple, the wife (who had been diagnosed with simple virilizing CAH at the age of 14 years, based on clinical and metabolic profile) was identified with c.373C >T variant on one and a deletion on the other allele of CYP21A2. Her asymptomatic husband harbored a novel c. 939+5G>A variant in intron 7 of CYP21A2. Prenatal diagnosis by Sanger sequencing revealed the presence of both maternal (c.373C>T) and paternal (c. 939+5G>A) variants in the fetus, indicative of SV form. After genetic counseling, the parents decided to continue with the pregnancy. Management and Outcome: A baby boy was born who underwent investigations according to the standard protocol. However, a diagnosis of CAH could not be established conclusively. The molecular diagnosis of both baby and parents was revisited. It was found that the baby harbored a duplication of CYP21A2 (inherited from his father) along with a novel variant. The duplication neutralized the paternal variant, and thus the baby was not affected, but a carrier. Conclusion: Evaluation of duplication in parents is crucial before prenatal testing, as duplications have important bearing on the carrier status.

Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)

 Article Access Statistics
    PDF Downloaded20    
    Comments [Add]    

Recommend this journal