Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase Deficiency
Steroid 11β-hydroxylase deficiency (11β-OHD) is the second most common cause of congenital adrenal hyperplasia. Mutations in the CYP11B1 gene, which encodes steroid 11β-hydroxylase, are responsible for this autosomal recessive disorder. Here, we describe the molecular genetics of two previously rep...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2014/185974 |
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| author | Katja Dumic Tony Yuen Zorana Grubic Vesna Kusec Ingeborg Barisic Maria I. New |
| author_facet | Katja Dumic Tony Yuen Zorana Grubic Vesna Kusec Ingeborg Barisic Maria I. New |
| author_sort | Katja Dumic |
| collection | DOAJ |
| description | Steroid 11β-hydroxylase deficiency (11β-OHD) is the second most common cause of congenital adrenal hyperplasia. Mutations in the CYP11B1 gene, which encodes steroid 11β-hydroxylase, are responsible for this autosomal recessive disorder. Here, we describe the molecular genetics of two previously reported male siblings in whom diagnosis of 11β-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 11β-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 11β-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. |
| format | Article |
| id | doaj-art-fee902ffd99a4f7291d7f267b7cd5fb1 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
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| series | International Journal of Endocrinology |
| spelling | doaj-art-fee902ffd99a4f7291d7f267b7cd5fb12025-02-03T05:51:59ZengWileyInternational Journal of Endocrinology1687-83371687-83452014-01-01201410.1155/2014/185974185974Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase DeficiencyKatja Dumic0Tony Yuen1Zorana Grubic2Vesna Kusec3Ingeborg Barisic4Maria I. New5Division of Clinical Genetics, Department of Pediatrics, Children’s University Hospital Zagreb, Klaiceva 16, 10000 Zagreb, CroatiaSteroid Disorder Program, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USATissue Typing Centre, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDepartment of Laboratory Medicine, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDivision of Clinical Genetics, Department of Pediatrics, Children’s University Hospital Zagreb, Klaiceva 16, 10000 Zagreb, CroatiaSteroid Disorder Program, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USASteroid 11β-hydroxylase deficiency (11β-OHD) is the second most common cause of congenital adrenal hyperplasia. Mutations in the CYP11B1 gene, which encodes steroid 11β-hydroxylase, are responsible for this autosomal recessive disorder. Here, we describe the molecular genetics of two previously reported male siblings in whom diagnosis of 11β-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 11β-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 11β-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.http://dx.doi.org/10.1155/2014/185974 |
| spellingShingle | Katja Dumic Tony Yuen Zorana Grubic Vesna Kusec Ingeborg Barisic Maria I. New Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase Deficiency International Journal of Endocrinology |
| title | Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase Deficiency |
| title_full | Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase Deficiency |
| title_fullStr | Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase Deficiency |
| title_full_unstemmed | Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase Deficiency |
| title_short | Two Novel CYP11B1 Gene Mutations in Patients from Two Croatian Families with 11β-Hydroxylase Deficiency |
| title_sort | two novel cyp11b1 gene mutations in patients from two croatian families with 11β hydroxylase deficiency |
| url | http://dx.doi.org/10.1155/2014/185974 |
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