Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11 β -Hydroxylase Deficiency.

[congenital adrenal hyperplasia]

Steroid 11 β -hydroxylase deficiency (11 β -OHD ) is the second most common cause of congenital adrenal hyperplasia . Mutations in the CYP 11 B 1 gene , which encodes steroid 11 β -hydroxylase , are responsible for this autosomal recessive disorder . Here , we describe the molecular genetics of two previously reported male siblings in whom diagnosis of 11 β -OHD has been established based on their hormonal profiles displaying high levels of 11 -deoxycortisol and hyperandrogenism . Both patients are compound heterozygous for a novel p .E 67 fs (c .199 delG ) mutation in exon 1 and a p .R 448 H (c .1343 G >A ) mutation in exon 8 . We also report the biochemical and molecular genetics data of one new 11 β -OHD patient . Sequencing of the CYP 11 B 1 gene reveals that this patient is compound heterozygous for a novel , previously undescribed p .R 141 Q (c .422 G >A ) mutation in exon 3 and a p .T 318 R (c .953 C >G ) mutation in exon 5 . All three patients are of Croatian (Slavic ) origin and there is no self-reported consanguinity in these two families . Results of our investigation confirm that most of the CYP 11 B 1 mutations are private . In order to elucidate the molecular basis for 11 β -OHD in the Croatian /Slavic population , it is imperative to perform CYP 11 B 1 genetic analysis in more patients from this region , since so far only four patients from three unrelated Croatian families have been analyzed .