Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita
| العنوان: | Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita |
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| المؤلفون: | Merryn V. E. Macville, David Hunt, Richard Webster, Suzanna G.M. Frints, Alberto Fernández-Jaén, Shelagh Joss, Andrew G. L. Douglas, Margje Sinnema, Lesley M McGregor, Vera M. Kalscheuer, Abhijit Dixit, Paulien A. Terhal, Arthur Lee, Sébastien Jacquemont, Omar A. Abdul-Rahman, Peter Wieacker, Koen L.I. van Gassen, Norbert Utzig, Marcus Lee, Vanessa Suckow, Gunnar Houge, Danita Velasco, Cheryl Longman, Holly H. Zimmerman, Elizabeth C. Engle, Bryce A. Mendelsohn, Salwan Al-Nasiry, Suzanne M. Koudijs, Saskia M. Maas, Diana Baralle, Hiromi Hirata, Kees E. P. van Roozendaal, Servi J. C. Stevens, Raoul C.M. Hennekam, Roberto Colombo, Ulrike Kordaß, Gyri Aasland Gradek, Friederike Hennig |
| المساهمون: | APH - Quality of Care, Human Genetics, Amsterdam Neuroscience - Complex Trait Genetics, MUMC+: DA KG Bedrijfsbureau (9), Klinische Genetica, MUMC+: DA KG Polikliniek (9), MUMC+: DA KG Lab Centraal Lab (9), Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: MA Med Staf Spec Neurologie (9) |
| المصدر: | Human Mutation, 40(12), 2270-2285. Wiley-Liss Inc. Human mutation, 40(12), 2270-2285. Wiley-Liss Inc. Human Mutation Human Mutation, 40(12), 2270-2285. Wiley Human Mutation, 40(12), 2270. Wiley-Liss Inc. Hum Mutat |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, INTELLECTUAL DISABILITY, Enfermedad del sistema nervioso, CONTRACTURES, Pie zambo, Genes, X-Linked, Missense mutation, Genetics(clinical), Frameshift Mutation, EXCHANGE, Zebrafish, Genetics (clinical), Sequence Deletion, media_common, Arthrogryposis, Genetics, Sex Characteristics, Paraplejía, medicine.diagnostic_test, 2 microdeletion, Intracellular Signaling Peptides and Proteins, complicated spastic paraplegia/ spasticity, METHYLATION, Espasticidad muscular, Nuclear Proteins, spasticity, Phenotype, Pedigree, Codon, Nonsense, akinesia, Female, Neurogenic arthrogryposis multiplex congenita, media_common.quotation_subject, fetal hypo, Nonsense, Mutation, Missense, Biology, DIAGNOSIS, Article, Frameshift mutation, medicine, Animals, Humans, Genetic Predisposition to Disease, Gene, Genetic testing, ZC4H2-Associated Rare Disorders (ZARD), SPECTRUM, Arthrogryposis multiplex congenita, MUTATIONS, fetal hypo-/akinesia, feet, club foot/-feet, ZC4H2, GENE, Genética, DELETIONS, Disease Models, Animal, complicated spastic paraplegia, Mutation, Xq11.2 microdeletion, Xq11, MENTAL-RETARDATION, club foot |
| الوصف: | Pathogenic variants in the X-linked gene ZC4H2, which encodes a zinc-finger protein, cause an infrequently described syndromic form of arthrogryposis multiplex congenita (AMC) with central and peripheral nervous system involvement. We present genetic and detailed phenotypic information on 23 newly identified families and simplex cases that include 19 affected females from 18 families and 14 affected males from nine families. Of note, the 15 females with deleterious de novo ZC4H2 variants presented with phenotypes ranging from mild to severe, and their clinical features overlapped with those seen in affected males. By contrast, of the nine carrier females with inherited ZC4H2 missense variants that were deleterious in affected male relatives, four were symptomatic. We also compared clinical phenotypes with previously published cases of both sexes and provide an overview on 48 males and 57 females from 42 families. The spectrum of ZC4H2 defects comprises novel and recurrent mostly inherited missense variants in affected males, and de novo splicing, frameshift, nonsense, and partial ZC4H2 deletions in affected females. Pathogenicity of two newly identified missense variants was further supported by studies in zebrafish. We propose ZC4H2 as a good candidate for early genetic testing of males and females with a clinical suspicion of fetal hypo-/akinesia and/or (neurogenic) AMC. Sin financiación 4.124 JCR (2019) Q1, 45/178 Genetics & Heredity 2.410 SJR (2019) Q1, 43/356 Genetics No data IDR 2019 UEM |
| وصف الملف: | image/pdf; application/pdf; text/plain; text |
| اللغة: | English |
| تدمد: | 1059-7794 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e587a6c9800551eea35560a0b6cc9e0a https://hdl.handle.net/11268/10551 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e587a6c9800551eea35560a0b6cc9e0a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10597794 |
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