title: Analysis of FMR1 gene premutation and X chromosome cytogenetic abnormalities in 100 Tunisian patients presenting premature ovarian failure.
abstract: OBJECTIVE
  To evaluate the prevalence of FMR1 premutations and X chromosome cytogenetic abnormalities in a large cohort of Tunisian women with premature ovarian failure (POF).
  
  
  METHODS
  The cohort consisted of 127 Tunisian women with POF referred by endocrinologists and gynecologists for genetic investigation in the context of idiopathic POF and altered hormonal profiles. Clinical information concerning the reproductive function in the family, previous hormonal measurements and/or possible fertility treatment were collected. Karyotype, FISH analyses, FMR1 and FMR2 testing were performed for all patients.
  
  
  RESULTS
  Fifteen patients (11.81%) presented structural or numerical X chromosomal abnormalities. Moreover, we detected in 12 patients (10.71%) a high level of X mosaicism. Analysis of FMR1 gene in the 100 patients without X chromosomal abnormalities showed that five percent of the patients carried a FMR1 premutation allele. On the other hand, the FMR2 screening did not reveal any deletion.
  
  
  CONCLUSIONS
  Our study confirms the major role of X chromosome abnormalities in POF and highlights the importance of karyotype analyses and FMR1 screening. These investigations provide valuable information for diagnosis and genetic counseling for these women who still have a 5% chance of spontaneous conception.
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia. Electronic address: nouha_bmail@yahoo.fr.
authors.forename: Nouha
authors.initials: N
authors.lastname: Bouali
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Dorra
authors.initials: D
authors.lastname: Hmida
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Mougou
authors.affiliation: Inserm UMR_S1185, faculté de médecine Paris Sud, université Paris Saclay, université Paris sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre, France; Service de génétique moléculaire, pharmacogénétique et hormonologie, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bouligand
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Besma
authors.initials: B
authors.lastname: Lakhal
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Sarra
authors.initials: S
authors.lastname: Dimessi
authors.affiliation: Inserm UMR_S1185, faculté de médecine Paris Sud, université Paris Saclay, université Paris sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre, France; Service de génétique moléculaire, pharmacogénétique et hormonologie, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Francou
authors.affiliation: Department of physiology and functional exploration, Farhat Hached university hospital, Sousse, Tunisia.
authors.forename: Ghada
authors.initials: G
authors.lastname: Saad
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Trabelsi
authors.affiliation: Department of physiology and functional exploration, Farhat Hached university hospital, Sousse, Tunisia.
authors.forename: Monia
authors.initials: M
authors.lastname: Zaouali
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Moez
authors.initials: M
authors.lastname: Gribaa
authors.affiliation: Endocrinology and diabetic service, CHU Farhat Hached of Sousse, Sousse, Tunisia.
authors.forename: Molka
authors.initials: M
authors.lastname: Chaieb
authors.affiliation: Gynecology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Mouhamed
authors.initials: M
authors.lastname: Bibi
authors.affiliation: Inserm UMR_S1185, faculté de médecine Paris Sud, université Paris Saclay, université Paris sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre, France; Service de génétique moléculaire, pharmacogénétique et hormonologie, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.affiliation: Laboratory of human cytogenetics, molecular genetics and reproductive biology, Farhat Hached university hospital, street Ibn El Jazzar, 4000 Sousse, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
mesh_terms: D000328:Adult; D000483:Alleles; D041321:Chromosomes, Human, X / Q000235:genetics; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007986:Luteinizing Hormone / Q000097:blood; D009030:Mosaicism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D012729:Sex Chromosome Aberrations; D014416:Tunisia
chemical_list: D004958:Estradiol; D005640:Follicle Stimulating Hormone; D051860:Fragile X Messenger Ribonucleoprotein 1; D007986:Luteinizing Hormone; D009687:Nuclear Proteins; C099930:AFF2 protein, human; C497683:FMR1 protein, human
keywords: Anomalies chromosomiques de l’X; FMR1 gene; Gène FMR1; Insuffisance ovarienne prématurée (IOP); Premature ovarian failure (POF); Premutation allele; Prémutation; X chromosome abnormalities