title: Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11 β -Hydroxylase Deficiency.
abstract: Steroid 11 β -hydroxylase deficiency (11 β -OHD) is the second most common cause of congenital adrenal hyperplasia. Mutations in the CYP11B1 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.E67fs (c.199delG) mutation in exon 1 and a p.R448H (c.1343G>A) mutation in exon 8. We also report the biochemical and molecular genetics data of one new 11 β -OHD patient. Sequencing of the CYP11B1 gene reveals that this patient is compound heterozygous for a novel, previously undescribed p.R141Q (c.422G>A) mutation in exon 3 and a p.T318R (c.953C>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 CYP11B1 mutations are private. In order to elucidate the molecular basis for 11 β -OHD in the Croatian/Slavic population, it is imperative to perform CYP11B1 genetic analysis in more patients from this region, since so far only four patients from three unrelated Croatian families have been analyzed.
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Children's University Hospital Zagreb, Klaiceva 16, 10000 Zagreb, Croatia.
authors.forename: Katja
authors.initials: K
authors.lastname: Dumic
authors.affiliation: Steroid Disorder Program, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Yuen
authors.affiliation: Tissue Typing Centre, University Hospital Centre Zagreb, 10000 Zagreb, Croatia.
authors.forename: Zorana
authors.initials: Z
authors.lastname: Grubic
authors.affiliation: Department of Laboratory Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Kusec
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Children's University Hospital Zagreb, Klaiceva 16, 10000 Zagreb, Croatia.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Barisic
authors.affiliation: Steroid Disorder Program, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: New