The Spectrum of Gene Mutations from 16 Families of Congenital Adrenal Hyperplasia: Genotype-Phenotype Correlation.

AIM

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of the adrenal steroidogenic pathway. The most common form of CAH is due to 21-hydroxylase deficiency resulting from mutations in gene. The present study aimed to identify common gene mutations, phenotype correlation, and to analyze the segregation pattern in CAH patients, parents, and siblings.

MATERIALS AND METHODS

Sixteen families having at least one classic CAH child in each family, a total of 58 subjects were recruited. The presence of six most common gene mutations, namely, Intron 2 (c.293-13A/C>G), c.844G>T (p.Val282Leu), c.1019G>A (p.Arg340His), c.92C>T (p.Pro31Leu), c.955C>T (p.Gln319*), and c.518T>A (p.Ile173Asn) in gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using specific primers.

RESULTS

Out of 16 classic CAH females analyzed, salt-wasting (SW) form was present in 12 (75%) and simple virilizing form in four (25%) children. Isolated clitoromegaly was the most common clinical presentation followed by ambiguous genitalia. The most common mutation observed in CAH patient population was Intron 2 (c.293-13A/C>G) (100%) followed by p.Pro31Leu (98%), p.Gln319* (93%), p.Val282Leu (91.4%), and p.Ile173Asn (19%). Although p.Arg340His mutation was not observed in this study. Interestingly, Intron 2 (c.293-13A/C>G) homozygous was observed in 31.3% of the entire study cohort and p.Ile173Asn mutation was found to be associated with SW form.

CONCLUSIONS

Our results suggested a high prevalence of gene mutations among CAH patients and heterogeneous mutation spectrum in their families of south Indian cohort. The outcomes afford valuable evidence for premarital and prenatal screening as well as planning suitable programs to prevent the development of CAH in Indian population.