Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants
| Autor: | Attila Nemeth, Christian De Geyter, Irene Halperin, Nicolas J Niederländer, Laura Marino, Cheng Xu, Nelly Pitteloud, Richard Quinton, Lucie Favre, Duarte Pignatelli, Georgios Papadakis, Daniele Cassatella, Andrew A. Dwyer, Katrin Feller, Almer M. van der Sloot, Philippe Maeder, Christa E. Flück, Deborah Bartholdi, Sandra Pekic Djurdjevic, James S Acierno, Michael Hauschild |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Proband Heterozygote medicine.medical_specialty Kallmann syndrome Disease 030105 genetics & heredity 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 Humans Hypogonadism/genetics Mutation Pedigree Phenotype Sequence Analysis DNA CHARGE syndrome chromodomain helicase DNA binding protein 7 congenital hypogonadotropic hypogonadism 03 medical and health sciences Internal medicine medicine 610 Medicine & health Genetics (clinical) Exome sequencing Genetics business.industry Hypogonadism DNA Helicases Genetic Variation Heterozygote advantage medicine.disease DNA-Binding Proteins 030104 developmental biology Endocrinology Medical genetics Congenital Hypogonadotropic Hypogonadism CHARGE Syndrome business |
| Zdroj: | Genetics in medicine, vol. 20, no. 8, pp. 872-881 |
| DOI: | 10.7892/boris.109627 |
| Popis: | PurposeCongenital 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.MethodsRare 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.ResultsOf 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).ConclusionPathogenic 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.Genetics in Medicine advance online publication, 16 November 2017; doi:10.1038/gim.2017.197. |
| Databáze: | OpenAIRE |
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