title: Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism.
abstract: OBJECTIVE
  Congenital hypopituitarism is a rare disease which, for most patients, has no identified molecular cause. We aimed to document the molecular basis of growth retardation in a Moroccan cohort.
  
  
  METHODS
  80 index cases [54 with isolated growth hormone deficiency (IGHD), 26 with combined pituitary hormone deficiency (CPHD)] were screened for molecular defects in GH1 (including LCR-GH1), GHRHR, GHSR, GHRH, PROP1, POU1F1, HESX1, LHX3, LHX4 and SOX3.
  
  
  RESULTS
  Five different deleterious mutations were identified in 14 patients from eight families. In the IGHD group, three genes were found to be involved: GH1, GHRHR and GHSR. In the CPHD group, PROP1 was the only mutated gene. In addition, two heterozygous variations whose deleterious effect remains to be demonstrated were identified (in GH1 and LHX4), and two polymorphisms (missense variations) were detected (in LHX3 and in GHSR). The prevalence of mutations in this Moroccan GHD cohort was 10% (8/80), 11·1% (6/54) in the IGHD group and 7·7% (2/26) in the CPHD group.
  
  
  CONCLUSIONS
  This is the first molecular screening of congenital GHD in a Moroccan population and, like other studies, mutations were preferentially identified in familial cases (75%); mutations in genes such as POU1F1, HESX1, SOX3, LHX3 and LHX4 are extremely rare. The p.R73C PROP1 mutation was the most frequent mutation in CPHD; this should be the first one to screen in this population. Our results should contribute to a better diagnosis and management of this heterogeneous disease condition.
authors.affiliation: Laboratory of Biochemistry-Immunology, Faculty of Science, Mohammed V University, Rabat, Morocco.
authors.forename: Nabila
authors.initials: N
authors.lastname: Fritez
authors.affiliation: Inserm UMRS933, Hôpital Trousseau, Paris, France.|UMRS933, Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Sobrier
authors.affiliation: Hôpital Ibn Sina, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco.
authors.forename: Hinde
authors.initials: H
authors.lastname: Iraqi
authors.affiliation: Inserm UMRS933, Hôpital Trousseau, Paris, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Vié-Luton
authors.affiliation: Service d'Endocrinologie Pédiatrique, AP-HP, Hôpital Trousseau, Paris, France.
authors.forename: Irène
authors.initials: I
authors.lastname: Netchine
authors.affiliation: Laboratory of Biochemistry-Immunology, Faculty of Science, Mohammed V University, Rabat, Morocco.
authors.forename: Abdessamad
authors.initials: A
authors.lastname: El Annas
authors.affiliation: Inserm U894, 2 ter rue d'Alesia, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Pantel
authors.affiliation: UF de Génétique Moléculaire, AP-HP, Hôpital Trousseau, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Collot
authors.affiliation: UF de Génétique Moléculaire, AP-HP, Hôpital Trousseau, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rose
authors.affiliation: UF de Génétique Moléculaire, AP-HP, Hôpital Trousseau, Paris, France.
authors.forename: William
authors.initials: W
authors.lastname: Piterboth
authors.affiliation: Inserm UMRS933, Hôpital Trousseau, Paris, France.|UF de Génétique Moléculaire, AP-HP, Hôpital Trousseau, Paris, France.|UMRS933, Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Legendre
authors.affiliation: Hôpital Ibn Sina, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco.
authors.forename: Abdelmjid
authors.initials: A
authors.lastname: Chraibi
authors.affiliation: Inserm UMRS933, Hôpital Trousseau, Paris, France.|UF de Génétique Moléculaire, AP-HP, Hôpital Trousseau, Paris, France.|UMRS933, Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
authors.affiliation: Hôpital Ibn Sina, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco.
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Kadiri
authors.affiliation: Laboratory of Biochemistry-Immunology, Faculty of Science, Mohammed V University, Rabat, Morocco.
authors.forename: Latifa
authors.initials: L
authors.lastname: Hilal
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000235:genetics; D008297:Male; D009018:Morocco; D009154:Mutation; D015995:Prevalence
chemical_list: D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D019382:Human Growth Hormone