Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants.

Détails

ID Serval
serval:BIB_88754A56C4C4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants.
Périodique
Genetics in medicine
Auteur(s)
Xu C., Cassatella D., van der Sloot A.M., Quinton R., Hauschild M., De Geyter C., Flück C., Feller K., Bartholdi D., Nemeth A., Halperin I., Pekic Djurdjevic S., Maeder P., Papadakis G., Dwyer A.A., Marino L., Favre L., Pignatelli D., Niederländer N.J., Acierno J., Pitteloud N.
ISSN
1530-0366 (Electronic)
ISSN-L
1098-3600
Statut éditorial
Publié
Date de publication
08/2018
Peer-reviewed
Oui
Volume
20
Numéro
8
Pages
872-881
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Congenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined.
Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated.
Of the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibit multiple CHARGE features, and 3 of these patients were reclassified as having CHARGE syndrome. In contrast, only 8% (1/12) of CHH patients with nonpathogenic CHD7 variants exhibited multiple CHARGE features (P = 0.01).
Pathogenic or likely pathogenic CHD7 variants rarely cause isolated CHH. Therefore a detailed clinical investigation is indicated to clarify the diagnosis (CHH versus CHARGE) and to optimize clinical management.
Mots-clé
CHARGE Syndrome/diagnosis, CHARGE Syndrome/genetics, DNA Helicases/genetics, DNA Helicases/metabolism, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Family, Female, Genetic Association Studies, Genetic Variation/genetics, Heterozygote, Humans, Hypogonadism/genetics, Male, Mutation, Pedigree, Phenotype, Sequence Analysis, DNA, CHARGE syndrome, Kallmann syndrome, chromodomain helicase DNA binding protein 7, congenital hypogonadotropic hypogonadism
Pubmed
Web of science
Création de la notice
24/09/2018 10:52
Dernière modification de la notice
20/08/2019 14:47
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