Hypopituitarism in Patients with Blepharophimosis and FOXL2 Mutations.


Journal

Hormone research in paediatrics
ISSN: 1663-2826
Titre abrégé: Horm Res Paediatr
Pays: Switzerland
ID NLM: 101525157

Informations de publication

Date de publication:
2020
Historique:
received: 12 11 2019
accepted: 15 03 2020
pubmed: 27 5 2020
medline: 20 4 2021
entrez: 27 5 2020
Statut: ppublish

Résumé

FOXL2 is the gene involved in blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). There have been few single case reports of growth hormone deficiency (GHD) with this syndrome, and Foxl2 is known to be involved in pituitary development in mice. Our aim was to analyze the prevalence of FOXL2 gene alteration in a series of patients with congenital hypopituitarism and eyelid anomalies. FOXL2 was analyzed in 10 patients with hypopituitarism (ranging from isolated GHD to complete pituitary hormone deficiency) and eyelid anomalies (typical BPES in 4 patients and milder anomalies in 6 patients). In patients with an FOXL2 mutation, we ruled out other possible molecular explanations by analyzing a panel of 20 genes known to be associated with hypopituitarism, and a candidate gene approach was used for patients without an FOXL2mutation. Three patients had an FOXL2mutation. All 3 had typical BPES. Their pituitary phenotype varied from GHD to complete pituitary hormone deficiency and their pituitary morphology ranged from normal to an interrupted pituitary stalk. No mutations were found in genes previously associated with hypopituitarism. Our study shows that some patients with BPES have hypopituitarism with no molecular explanation other than FOXL2 mutation. This points toward an involvement of FOXL2 in human pituitary development.

Sections du résumé

BACKGROUND BACKGROUND
FOXL2 is the gene involved in blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). There have been few single case reports of growth hormone deficiency (GHD) with this syndrome, and Foxl2 is known to be involved in pituitary development in mice. Our aim was to analyze the prevalence of FOXL2 gene alteration in a series of patients with congenital hypopituitarism and eyelid anomalies.
METHODS METHODS
FOXL2 was analyzed in 10 patients with hypopituitarism (ranging from isolated GHD to complete pituitary hormone deficiency) and eyelid anomalies (typical BPES in 4 patients and milder anomalies in 6 patients). In patients with an FOXL2 mutation, we ruled out other possible molecular explanations by analyzing a panel of 20 genes known to be associated with hypopituitarism, and a candidate gene approach was used for patients without an FOXL2mutation.
RESULTS RESULTS
Three patients had an FOXL2mutation. All 3 had typical BPES. Their pituitary phenotype varied from GHD to complete pituitary hormone deficiency and their pituitary morphology ranged from normal to an interrupted pituitary stalk. No mutations were found in genes previously associated with hypopituitarism.
CONCLUSION CONCLUSIONS
Our study shows that some patients with BPES have hypopituitarism with no molecular explanation other than FOXL2 mutation. This points toward an involvement of FOXL2 in human pituitary development.

Identifiants

pubmed: 32454486
pii: 000507249
doi: 10.1159/000507249
doi:

Substances chimiques

Forkhead Box Protein L2 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

30-39

Informations de copyright

© 2020 S. Karger AG, Basel.

Auteurs

Sarah Castets (S)

Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d'Endocrinologie Pédiatrique, Bron, France, sarah.castets@gmail.com.
Aix-Marseille Université, AP-HM, Centre de Référence des Maladies Rares D'origine Hypophysaire HYPO, Marseille, France, sarah.castets@gmail.com.

Florence Roucher-Boulez (F)

Hospices Civils de Lyon, Groupement Hospitalier Est, Laboratoire de Biochimie et Biologie Moléculaire Grand Est, UM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Bron, France.
Centre de Référence du Développement Génital: du Fœtus à l'Adulte, Filière Maladies Rares Endocriniennes, Bron, France.
Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.

Alexandru Saveanu (A)

Aix-Marseille Université, AP-HM, Centre de Référence des Maladies Rares D'origine Hypophysaire HYPO, Marseille, France.
Aix Marseille Université, INSERM, MMG, U 1251, Marseille, France.

Delphine Mallet-Motak (D)

Hospices Civils de Lyon, Groupement Hospitalier Est, Laboratoire de Biochimie et Biologie Moléculaire Grand Est, UM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Bron, France.
Centre de Référence du Développement Génital: du Fœtus à l'Adulte, Filière Maladies Rares Endocriniennes, Bron, France.

Olivier Chabre (O)

CHU de Grenoble Alpes et Université Grenoble Alpes, CS 10217 38043, Service d'Endocrinologie, Grenoble, France.

Patrizia Amati-Bonneau (P)

MitoLab Team, UMR CNRS 6015 - INSERM U1083, Institut MitoVasc, Université et Hôpital d'Angers, Angers, France.
Département de Biochimie et Génétique, Université et Hôpital d'Angers, Angers, France.

Dominique Bonneau (D)

MitoLab Team, UMR CNRS 6015 - INSERM U1083, Institut MitoVasc, Université et Hôpital d'Angers, Angers, France.
Département de Biochimie et Génétique, Université et Hôpital d'Angers, Angers, France.

Celine Girardin (C)

Hôpitaux Universitaires de Genève, Endocrinologie Pédiatrique, Genève, Switzerland.

Yves Morel (Y)

Hospices Civils de Lyon, Groupement Hospitalier Est, Laboratoire de Biochimie et Biologie Moléculaire Grand Est, UM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Bron, France.
Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.

Carine Villanueva (C)

Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d'Endocrinologie Pédiatrique, Bron, France.
Centre de Référence du Développement Génital: du Fœtus à l'Adulte, Filière Maladies Rares Endocriniennes, Bron, France.

Thierry Brue (T)

Aix-Marseille Université, AP-HM, Centre de Référence des Maladies Rares D'origine Hypophysaire HYPO, Marseille, France.
Aix Marseille Université, INSERM, MMG, U 1251, Marseille, France.

Rachel Reynaud (R)

Aix-Marseille Université, AP-HM, Centre de Référence des Maladies Rares D'origine Hypophysaire HYPO, Marseille, France.
Aix Marseille Université, INSERM, MMG, U 1251, Marseille, France.

Marc Nicolino (M)

Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d'Endocrinologie Pédiatrique, Bron, France.
Centre de Référence du Développement Génital: du Fœtus à l'Adulte, Filière Maladies Rares Endocriniennes, Bron, France.
Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.

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Classifications MeSH