title: High prevalence of PROP1 defects in Lithuania: phenotypic findings in an ethnically homogenous cohort of patients with multiple pituitary hormone deficiency.
abstract: BACKGROUND
  PROP1 gene mutations cause multiple pituitary hormone deficiency (MPHD).
  
  
  OBJECTIVE
  We sought to expand experience with PROP1 mutation carriers by studying a large cohort of Lithuanian patients.
  
  
  METHODS
  Sixty-seven MPHD patients were tested for PROP1 defects. Perinatal and postnatal data were obtained from medical records. Hormonal investigations, pituitary imaging, and GH therapy were provided in a single center in Kaunas, Lithuania.
  
  
  RESULTS
  A biallelic PROP1 gene mutation was found in 47 subjects (70.1%), of which 46 were homozygous for 296delGA. Positive finding rate among MPHD and population prevalence of PROP1 defects in Lithuania (15.8 per million) were the highest reported to date. Patients' birth lengths/weights were normal. Testicular retention was noted in 31% of boys. Median height SD scores declined over years 1-5: -1.56, -2.34, -3.43, -3.52, and -3.70. Mid-parental height predicted severity of growth retardation at diagnosis (r2=0.30; P=.0001). Deficiencies of GH, TSH, ACTH, and FSH/LH were diagnosed in 44/44, 44/44, 19/44, and 22/44 subjects at median age of 5.5, 5.6, 13.1, and 15.0 years, respectively. Pituitary height ranged from 16.6 mm (+20.2 SD) to 1.4 mm (-15.5 SD) and declined with age (r2=0.27, P=.001). GH replacement (dose 0.027 mg/kg/d) led to height velocities 12.2; 9.1; 6.9; 6.8; 6.7; 5.6; and 5.7 cm/y (medians) at years 1-7 and final height SD scores (17 patients) -0.98±1.77 (-1.04±1.41 below target height; P=.008 vs 0).
  
  
  CONCLUSIONS
  High prevalence of PROP1 defects in Lithuania is due to 296delGA mutation, suggesting a founder effect.
authors.affiliation: Institute of Endocrinology (R.N., N.S., R.V.), Medical Academy (D.A.), Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania; Department of Pediatrics (P.D., B.O., O.C., J.L.), Second Faculty of Medicine, Charles University in Prague and University Hospital Prague-Motol, 150 06 Prague, Czech Republic; and University Hospital for Children and Adolescents (R.W.F., W.F.B.), University of Leipzig, 04317 Leipzig, Germany.
authors.forename: Ruta
authors.initials: R
authors.lastname: Navardauskaite
authors.forename: Petra
authors.initials: P
authors.lastname: Dusatkova
authors.forename: Barbora
authors.initials: B
authors.lastname: Obermannova
authors.forename: Roland W
authors.initials: RW
authors.lastname: Pfaeffle
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Dalia
authors.initials: D
authors.lastname: Adukauskiene
authors.forename: Natalija
authors.initials: N
authors.lastname: Smetanina
authors.forename: Ondrej
authors.initials: O
authors.lastname: Cinek
authors.forename: Rasa
authors.initials: R
authors.lastname: Verkauskiene
authors.forename: Jan
authors.initials: J
authors.lastname: Lebl
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007018:Hypopituitarism / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D007223:Infant; D008097:Lithuania / Q000453:epidemiology; D008297:Male; D010641:Phenotype; D010902:Pituitary Gland / Q000000981:diagnostic imaging / Q000473:pathology; D010907:Pituitary Hormones / Q000172:deficiency*; D015995:Prevalence; D011859:Radiography; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; D010907:Pituitary Hormones; C102134:Prophet of Pit-1 protein