title: Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study.
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.
authors.affiliation: Pediatric Endocrinology, Istanbul Faculy of Medicine, Istanbul University, Çapa, Istanbul, 34093, Turkey, firdevsb@istanbul.edu.tr.
authors.forename: Firdevs
authors.initials: F
authors.lastname: Baş
authors.forename: Z Oya
authors.initials: ZO
authors.lastname: Uyguner
authors.forename: Feyza
authors.initials: F
authors.lastname: Darendeliler
authors.forename: Zehra
authors.initials: Z
authors.lastname: Aycan
authors.forename: Ergun
authors.initials: E
authors.lastname: Çetinkaya
authors.forename: Merih
authors.initials: M
authors.lastname: Berberoğlu
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Şiklar
authors.forename: Gönül
authors.initials: G
authors.lastname: Öcal
authors.forename: Şükran
authors.initials: Ş
authors.lastname: Darcan
authors.forename: Damla
authors.initials: D
authors.lastname: Gökşen
authors.forename: Ali Kemal
authors.initials: AK
authors.lastname: Topaloğlu
authors.forename: Bilgin
authors.initials: B
authors.lastname: Yüksel
authors.forename: Mehmet Nuri
authors.initials: MN
authors.lastname: Özbek
authors.forename: Oya
authors.initials: O
authors.lastname: Ercan
authors.forename: Olcay
authors.initials: O
authors.lastname: Evliyaoğlu
authors.forename: Semra
authors.initials: S
authors.lastname: Çetinkaya
authors.forename: Yaşar
authors.initials: Y
authors.lastname: Şen
authors.forename: Emre
authors.initials: E
authors.lastname: Atabek
authors.forename: Güven
authors.initials: G
authors.lastname: Toksoy
authors.forename: Banu Küçükemre
authors.initials: BK
authors.lastname: Aydin
authors.forename: Rüveyde
authors.initials: R
authors.lastname: Bundak
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics*; D007223:Infant; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D010375:Pedigree; D050817:Transcription Factor Pit-1 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014421:Turkey; D055815:Young Adult
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; C494187:POU1F1 protein, human; C102134:Prophet of Pit-1 protein; D050817:Transcription Factor Pit-1; D014157:Transcription Factors