Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2
| العنوان: | Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2 |
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| المؤلفون: | Jonathan Rodgers, Antonia Marchese, Frances Elmslie, Claudine Rieubland, Noriko Miyake, Sophie Julia, Ingrid Scurr, Emmanuel Scalais, Diana S. Johnson, Elise Brischoux-Boucher, Melissa Byler, Lisa Bradley, Julie McGaughran, Siddharth Banka, Maria Gnazzo, Robert Roger Lebel, Stephanie Goh, Damien Lederer, Jane A. Hurst, Maria Cristina Digilio, Ineke van der Burgt, Nobuhiko Okamoto, Mohnish Suri, Víctor Faundes, Rhoda Akilapa, Harinder Gill, Hans T. Bjornsson, Edmond G. Lemire, Saskia Bulk, Katherine Lachlan, Han G. Brunner, Andrew E. Fry, Eric Gershon, Maria Lisa Dentici, Erina Sasaki, Valérie Benoit, Heidre Bezuidenhout, Natalie Canham, Naomichi Matsumoto, Angela F. Brady, Declan Cody, Meriel McEntagart, Seiji Mizuno, Francesca Romana Lepri |
| المصدر: | Web of Science Faundes, V, Goh, S, Akilapa, R, Bezuidenhout, H, Bjornsson, H T, Brady, A F, Brischoux-Boucher, E, Brunner, H, Bulk, S, Canham, N, Cody, D, Dentici, M L, Digilio, M C, Elmslie, F, Fry, A E, Gill, H, Hurst, J, Johnson, D, Julia, S, Lachlan, K, Lebel, R R, Byler, M, Gershon, E, Lemire, E, Gnazzo, M, Lepri, F R, Marchese, A, McEntagart, M, McGaughran, J, Mizuno, S, Okamoto, N, Rieubland, C, Sasaki, E, Scalais, E, Scurr, I, Suri, M, van der Burgt, I, Matsumoto, N, Miyake, N, Benoit, V, Lederer, D & Banka, S 2021, ' Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2 ', Genetics in Medicine . https://doi.org/10.1038/s41436-021-01119-8Test Genetics in Medicine Genetics in Medicine, 23, 7, pp. 1202-1210 Genetics in Medicine, 23, 1202-1210 Faundes, Víctor; Goh, Stephanie; Akilapa, Rhoda; Bezuidenhout, Heidre; Bjornsson, Hans T; Bradley, Lisa; Brady, Angela F; Brischoux-Boucher, Elise; Brunner, Han; Bulk, Saskia; Canham, Natalie; Cody, Declan; Dentici, Maria Lisa; Digilio, Maria Cristina; Elmslie, Frances; Fry, Andrew E; Gill, Harinder; Hurst, Jane; Johnson, Diana; Julia, Sophie; ... (2021). Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2. Genetics in medicine, 23(7), pp. 1202-1210. Springer Nature 10.1038/s41436-021-01119-8 <http://dx.doi.org/10.1038/s41436-021-01119-8Test> |
| بيانات النشر: | Springer Nature, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Joint hypermobility, Microcephaly, Hearing loss, 610 Medicine & health, 030105 genetics & heredity, Biology, Article, 03 medical and health sciences, Intellectual Disability, Intellectual disability, medicine, Humans, Missense mutation, Abnormalities, Multiple, Genetic Association Studies, Genetics (clinical), Histone Demethylases, Genetics, Sex Characteristics, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Variant type, Infant, Newborn, medicine.disease, Hematologic Diseases, Phenotype, Neoplasm Proteins, DNA-Binding Proteins, 030104 developmental biology, Vestibular Diseases, Face, Female, medicine.symptom, Kabuki syndrome |
| الوصف: | Contains fulltext : 237823.pdf (Publisher’s version ) (Open Access) PURPOSE: The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood. METHODS: Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed. RESULTS: Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID. CONCLUSION: We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1. |
| وصف الملف: | application/pdf |
| تدمد: | 1098-3600 1530-0366 1202-1210 |
| DOI: | 10.48350/162645 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dbf9501e03c8ad1cdd39bcc6f535c4fbTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dbf9501e03c8ad1cdd39bcc6f535c4fb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10983600 15300366 12021210 |
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| DOI: | 10.48350/162645 |