Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency
Objective:Mutations of the genes encoding transcription factors which play important roles in pituitary morphogenesis, differentiation and maturation may lead to combined pituitary hormone deficiency (CPHD). PROP1 gene mutations are reported as the most frequent genetic aetiology of CHPD. The aim of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Galenos Yayincilik
2020-09-01
|
| Series: | JCRPE |
| Subjects: | |
| Online Access: |
http://www.jcrpe.org/archives/archive-detail/article-preview/mutations-within-the-transcription-factor-iprop1-i/34597
|
| _version_ | 1797920646385106944 |
|---|---|
| author | Fatma Derya Bulut Semine Özdemir Dilek Damla Kotan Eda Mengen Fatih Gürbüz Bilgin Yüksel |
| author_facet | Fatma Derya Bulut Semine Özdemir Dilek Damla Kotan Eda Mengen Fatih Gürbüz Bilgin Yüksel |
| author_sort | Fatma Derya Bulut |
| collection | DOAJ |
| description | Objective:Mutations of the genes encoding transcription factors which play important roles in pituitary morphogenesis, differentiation and maturation may lead to combined pituitary hormone deficiency (CPHD). PROP1 gene mutations are reported as the most frequent genetic aetiology of CHPD. The aim of this study was to describe the phenotypes of Turkish CPHD patients and define the frequency of PROP1 mutations.Methods:Fifty-seven CPHD patients from 50 families were screened for PROP1 mutations. The patients were affected by growth hormone (GH) and additional anterior pituitary hormone deficiencies.Results:All patients had GH deficiency. In addition, 98.2% had central hypothyroidism, 45.6% had hypogonadotropic hypogonadism, 43.8% had adrenocorticotropic hormone deficiency and 7.1% had prolactin deficiency. Parental consanguinity rate was 50.9% and 14 cases were familial. Mean height standard deviation score (SDS) and weight SDS were -3.8±1.4 and -3.1±2.0, respectively. Of 53 patients with available pituitary imaging, 32 (60.4%) showed abnormalities. None had extra-pituitary abnormalities. Eight index patients had PROP1 gene mutations. Five sporadic patients were homozygous for c.301_302delAG (p.Leu102CysfsTer8) mutation, two siblings had exon 2 deletion, two siblings had complete gene deletion and two siblings were homozygous for the novel c.353A>G (p.Q118R) mutation. The frequency of the PROP1 mutations was 16% in our cohort. Mutation rate was significantly higher in familial cases compared to sporadic cases (42.8% vs 11.6%; p<0.01).Conclusion:Phenotype of patients regarding hormonal deficiencies, pituitary morphology, presence of extra-pituitary findings, family history of CPHD and parental consanguinity are important for deciding which pituitary transcription factor deficiency should be investigated. PROP1 mutation frequencies vary in different populations and its prevalence is high in Turkish CPHD patients. |
| first_indexed | 2024-04-10T14:05:44Z |
| format | Article |
| id | doaj.art-834c2557d203484c97842279ba83d755 |
| institution | Directory Open Access Journal |
| issn | 1308-5727 1308-5735 |
| language | English |
| last_indexed | 2024-04-10T14:05:44Z |
| publishDate | 2020-09-01 |
| publisher | Galenos Yayincilik |
| record_format | Article |
| series | JCRPE |
| spelling | doaj.art-834c2557d203484c97842279ba83d7552023-02-15T16:10:03ZengGalenos YayincilikJCRPE1308-57271308-57352020-09-0112326126810.4274/jcrpe.galenos.2020.2019.019113049054Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone DeficiencyFatma Derya Bulut0Semine Özdemir Dilek1Damla Kotan2Eda Mengen3Fatih Gürbüz4Bilgin Yüksel5 Adana City Training and Research Hospital, Clinic of Pediatrics, Adana, Turkey Çukurova University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Adana, Turkey Çukurova University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Adana, Turkey Ankara City Hospital, Children’s Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey Çukurova University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Adana, Turkey Çukurova University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Adana, Turkey Objective:Mutations of the genes encoding transcription factors which play important roles in pituitary morphogenesis, differentiation and maturation may lead to combined pituitary hormone deficiency (CPHD). PROP1 gene mutations are reported as the most frequent genetic aetiology of CHPD. The aim of this study was to describe the phenotypes of Turkish CPHD patients and define the frequency of PROP1 mutations.Methods:Fifty-seven CPHD patients from 50 families were screened for PROP1 mutations. The patients were affected by growth hormone (GH) and additional anterior pituitary hormone deficiencies.Results:All patients had GH deficiency. In addition, 98.2% had central hypothyroidism, 45.6% had hypogonadotropic hypogonadism, 43.8% had adrenocorticotropic hormone deficiency and 7.1% had prolactin deficiency. Parental consanguinity rate was 50.9% and 14 cases were familial. Mean height standard deviation score (SDS) and weight SDS were -3.8±1.4 and -3.1±2.0, respectively. Of 53 patients with available pituitary imaging, 32 (60.4%) showed abnormalities. None had extra-pituitary abnormalities. Eight index patients had PROP1 gene mutations. Five sporadic patients were homozygous for c.301_302delAG (p.Leu102CysfsTer8) mutation, two siblings had exon 2 deletion, two siblings had complete gene deletion and two siblings were homozygous for the novel c.353A>G (p.Q118R) mutation. The frequency of the PROP1 mutations was 16% in our cohort. Mutation rate was significantly higher in familial cases compared to sporadic cases (42.8% vs 11.6%; p<0.01).Conclusion:Phenotype of patients regarding hormonal deficiencies, pituitary morphology, presence of extra-pituitary findings, family history of CPHD and parental consanguinity are important for deciding which pituitary transcription factor deficiency should be investigated. PROP1 mutation frequencies vary in different populations and its prevalence is high in Turkish CPHD patients. http://www.jcrpe.org/archives/archive-detail/article-preview/mutations-within-the-transcription-factor-iprop1-i/34597 combined pituitary hormone deficiencyhypopituitarismpituitary transcription factorsprop1 gene |
| spellingShingle | Fatma Derya Bulut Semine Özdemir Dilek Damla Kotan Eda Mengen Fatih Gürbüz Bilgin Yüksel Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency JCRPE combined pituitary hormone deficiency hypopituitarism pituitary transcription factors prop1 gene |
| title | Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency |
| title_full | Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency |
| title_fullStr | Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency |
| title_full_unstemmed | Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency |
| title_short | Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency |
| title_sort | mutations within the transcription factor prop1 in a cohort of turkish patients with combined pituitary hormone deficiency |
| topic | combined pituitary hormone deficiency hypopituitarism pituitary transcription factors prop1 gene |
| url |
http://www.jcrpe.org/archives/archive-detail/article-preview/mutations-within-the-transcription-factor-iprop1-i/34597
|
| work_keys_str_mv | AT fatmaderyabulut mutationswithinthetranscriptionfactorprop1inacohortofturkishpatientswithcombinedpituitaryhormonedeficiency AT semineozdemirdilek mutationswithinthetranscriptionfactorprop1inacohortofturkishpatientswithcombinedpituitaryhormonedeficiency AT damlakotan mutationswithinthetranscriptionfactorprop1inacohortofturkishpatientswithcombinedpituitaryhormonedeficiency AT edamengen mutationswithinthetranscriptionfactorprop1inacohortofturkishpatientswithcombinedpituitaryhormonedeficiency AT fatihgurbuz mutationswithinthetranscriptionfactorprop1inacohortofturkishpatientswithcombinedpituitaryhormonedeficiency AT bilginyuksel mutationswithinthetranscriptionfactorprop1inacohortofturkishpatientswithcombinedpituitaryhormonedeficiency |