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Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study

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Abstract

To investigate the specific mutations in PROP1, POU1F1, LHX3, and HESX1 genes in patients with combined pituitary hormone deficiency (CPHD) in Turkey. Seventy-six patients with CPHD were included in this study. Based on clinical, hormonal, and neuro-radiological data, relevant transcription factor genes were evaluated by Sanger sequencing and multiplex ligation-dependent probe amplification. Total frequency of mutations was 30.9 % in patients with CPHD. Frequency was significantly higher in familial patients (p = 0.001). Three different types of mutations in PROP1 gene (complete gene deletion, c.301-302delAG, a novel mutation; IVS1+2T>G) were found in 12 unrelated patients (21.8 %). Mutations in PROP1 gene were markedly higher in familial than in sporadic cases (58.8 vs. 5.3 %, p < 0.001). Homozygous complete gene deletion was the most common mutation in PROP1 gene (8/12) and was identified in six familial patients. Four different homozygous mutations [p.Q4X, novel mutations; exons 1–2 deletion, p.V153F, p.I244S] were detected in POU1F1 gene. Central precocious puberty was firstly observed in a sporadic-male patient with homozygous POU1F1 (p.I244S) mutation. A homozygous mutation in HESX1 gene (p.R160H) was detected in one patient. This study is the first to investigate specific mutations in CPHD patients in Turkey. Complete deletion in PROP1 gene was the most common mutation encountered in patients with CPHD. We believe that the results of this study will contribute to the establishment of genetic screening strategies in Turkey, as well as to the studies on phenotype–genotype correlations and early diagnosis of CPHD patients.

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Acknowledgments

This work was supported by Scientific and Technological Research Institution of Turkey (Project Number: 106S277-SBAG-3488) and Scientific Research Projects Coordination Unit of Istanbul University (Project Number: 2871). The authors would like to thank Professor Olcay Neyzi, MD, of the Istanbul Faculty of Medicine, Istanbul University, for helpful discussions and critical reading of the manuscript.

Conflict of interest

The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Pediatric Endocrinology, Istanbul Faculy of Medicine, Istanbul University, Çapa, Istanbul, 34093, Turkey

    Firdevs Baş, Feyza Darendeliler, Banu Küçükemre Aydin & Rüveyde Bundak

  2. Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Z. Oya Uyguner & Güven Toksoy

  3. Pediatric Endocrinology, Dışkapı Education and Research Hospital, Ankara, Turkey

    Zehra Aycan & Ergun Çetinkaya

  4. Pediatric Endocrinology, Dr. Sami Ulus Children’s Health and Disease Education and Research Hospital, Ankara, Turkey

    Zehra Aycan & Semra Çetinkaya

  5. Pediatric Endocrinology, Faculty of Medicine, Ankara University, Ankara, Turkey

    Merih Berberoğlu, Zeynep Şiklar & Gönül Öcal

  6. Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey

    Şükran Darcan & Damla Gökşen

  7. Pediatric Endocrinology, Faculty of Medicine, Çukurova University, Adana, Turkey

    Ali Kemal Topaloğlu, Bilgin Yüksel & Mehmet Nuri Özbek

  8. Pediatric Endocrinology, Diyarbakır Education and Research Hospital, Diyarbakır, Turkey

    Mehmet Nuri Özbek

  9. Pediatric Endocrinology, Cerrahpaşa Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Oya Ercan & Olcay Evliyaoğlu

  10. Pediatric Endocrinology, Selçuk Faculty of Medicine, Selçuk University, Konya, Turkey

    Yaşar Şen

  11. Pediatric Endocrinology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Emre Atabek

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  1. Firdevs Baş
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  2. Z. Oya Uyguner
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Correspondence to Firdevs Baş.

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Baş F, Uyguner ZO and Darendeliler F have contributed equally to this work and could be considered as first authors.

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Baş, F., Uyguner, Z.O., Darendeliler, F. et al. Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study. Endocrine 49, 479–491 (2015). https://doi.org/10.1007/s12020-014-0498-1

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