title: Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency.
abstract: OBJECTIVE
  The HESX1 gene is essential in forebrain development and pituitary organogenesis, and its mutations are the most commonly identified genetic cause of septo-optic dysplasia (SOD). The PROP1 gene is involved in anterior pituitary cell lineage specification and is commonly implicated in non-syndromic combined pituitary hormone deficiency (CPHD). We aimed to assess the involvement of HESX1 and PROP1 mutations in a cohort of patients with SOD and CPHD.
  
  
  METHODS
  Six patients with sporadic SOD and 16 patients with CPHD from 14 pedigrees were screened for mutations in HESX1 and PROP1 genes by exon sequencing. Half of the CPHD patients had variable associated clinical characteristics, such as hearing loss, orofacial cleft, kidney disorder or developmental delay. Novel variants were evaluated in silico and verified in SNP databases.
  
  
  RESULTS
  A novel heterozygous p.Glu102Gly mutation in the HESX1 gene and a novel homozygous p.Arg121Thr mutation in the PROP1 gene were detected in 2 pedigrees with CPHD. A small previously reported deletion in PROP1 c.301_302delAG was detected in a separate patient with CPHD, in heterozygous state. No mutations were identified in patients with SOD.
  
  
  CONCLUSIONS
  Our results expand the spectrum of mutations implicated in CPHD. The frequency of 15% of the PROP1 mutations in CPHD was low, likely due to the clinical heterogeneity of the cohort.
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Avbelj Stefanija
authors.forename: Primož
authors.initials: P
authors.lastname: Kotnik
authors.forename: Nina
authors.initials: N
authors.lastname: Bratanič
authors.forename: Mojca
authors.initials: M
authors.lastname: Žerjav Tanšek
authors.forename: Sara
authors.initials: S
authors.lastname: Bertok
authors.forename: Nataša
authors.initials: N
authors.lastname: Bratina
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.forename: Katarina
authors.initials: K
authors.lastname: Trebušak Podkrajšek
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D025962:Septo-Optic Dysplasia / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D004247:DNA