English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder caused by mutations in the  CYP21A2 . Congenital nephrogenic diabetes insipidus (NDI) is a rare X-linked recessive or autosomal recessive disorder caused by mutations in either  AVPR2  or  AQP2 . Genotype-phenotype discordance caused by genetic mosaicism in CAH patients has not been reported, nor the concomitant CAH and NDI.    Case presentation  We investigated a patient with concomitant CAH and NDI from a consanguineous family. She (S-1) presented with clitoromegaly at 3 month of age, and polydipsia and polyuria at 13 month of age. Her parents and two elder sisters (S-2 and S-3) were clinically normal, but elevated levels of serum 17-hydroxyprogesterone (17-OHP) were observed in the mother and S-2. The coding region of  CYP21A2  and  AQP2  were analyzed by PCR-sequencing analysis to identify genetic defects. Two homozygous  CYP21A2  mutations (p.R357W and p.P454S) were identified in the proband and her mother and S-2. The apparent genotype-phenotype discordance was due to presence of small amount of wild-type  CYP21A2  alleles in S-1, S-2, and their mother’s genome, thus protecting them from development of classic form of 21OHD (C21OHD). A homozygous  AQP2  mutation (p.A147T) was also found in the patient. The patient was treated with hydrocortisone and hydrochlorothiazide. Her symptoms were improved with normal laboratory findings. The clitoromegaly is persisted.    Conclusions  Genetic mosaicism is a novel mechanism contributing to the genotype-phenotype discordance in 21OHD and small percentage of wild-type  CYP21A2  alleles may be sufficient to prevent phenotype development. This is a first report of concurrent 21OHD and NDI caused by simultaneous homozygous  CYP21A2  and  AQP2  mutations.

Phenotype heterogeneity of congenital adrenal hyperplasia due to genetic mosaicism and concomitant nephrogenic diabetes insipidus in a sibling