Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort

Francesca De Rienzo, Simona Mellone, Simonetta Bellone, Deepak Babu, Ileana Fusco, Flavia Prodam, Antonella Petri, Ranjith Muniswamy, Filippo De Luca, Mariacarolina Salerno, Patricia Momigliano-Richardi, Gianni Bona, Mara Giordano, Italian Study Group on Genetics of CPHD, Mauro Bozzola

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: Combined pituitary hormonal deficiency (CPHD) can result from mutations within genes that encode transcription factors. This study evaluated the frequency of mutations in these genes in a cohort of 144 unrelated Italian patients with CPHD and estimated the overall prevalence of mutations across different populations using a systematic literature review.

MATERIAL AND METHODS: A multicentre study of adult and paediatric patients with CPHD was performed. The PROP1, POU1F1, HESX1, LHX3 and LHX4 genes were analysed for the presence of mutations using direct sequencing. We systematically searched PubMed with no date restrictions for studies that reported genetic screening of CPHD cohorts. We only considered genetic screenings with at least 10 individuals. Data extraction was conducted in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

RESULTS: Global mutation frequency in Italian patients with CPHD was 2·9% (4/136) in sporadic cases and 12·5% (1/8) in familial cases. The worldwide mutation frequency for the five genes calculated from 21 studies was 12·4%, which ranged from 11·2% in sporadic to 63% in familial cases. PROP1 was the most frequently mutated gene in sporadic (6·7%) and familial cases (48·5%).

CONCLUSION: The frequency of defects in genes encoding pituitary transcription factors is quite low in Italian patients with CPHD and other western European countries, especially in sporadic patients. The decision of which genes should be tested and in which order should be guided by hormonal and imaging phenotype, the presence of extrapituitary abnormalities and the frequency of mutation for each gene in the patient-referring population.

Original languageEnglish
Pages (from-to)849-60
Number of pages12
JournalClinical Endocrinology
Issue number6
Publication statusPublished - Dec 2015


  • Female
  • Genetic Predisposition to Disease
  • Homeodomain Proteins
  • Humans
  • Hypopituitarism
  • Italy
  • LIM-Homeodomain Proteins
  • Male
  • Transcription Factor Pit-1
  • Transcription Factors
  • Journal Article
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Review


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