KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis
| العنوان: | KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis |
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| المؤلفون: | Norine Voisin, Frédéric Tran Mau-Them, Bruno Reversade, Damien Sanlaville, Charles Shaw-Smith, Qamariya Ambusaidi, Egle Preiksaitiene, Saumya Shekhar Jamuar, Glen R. Monroe, Angeline Lai, Alexandre Reymond, Michaël Wiederkehr, Jamel Chelly, Audrey Putoux, Bernd Roechert, Sylvain Pradervand, Caroline F. Wright, Peter M. van Hasselt, Loreta Cimbalistienė, Mais Hashem, Marguerite Neerman-Arbez, Gaetan Lesca, Vaidutis Kučinskas, Gijs van Haaften, Lim J. Ying, Fabienne Allias, Ioannis Xenarios, Laurent Guibaud, Wesam Kurdi, Tommaso Pippucci, Lucie Gueneau, Hanan E. Shamseldin, Julien Delafontaine, Carine Bonnard, Laima Ambrozaityte, Nicolas Guex, Fowzan S. Alkuraya, Richard J. Fish, Erica Schindewolf |
| المساهمون: | Roechert, Bernd, Xenarios, Ioannis, Neerman Arbez, Marguerite, DDD Study, ACS - Amsterdam Cardiovascular Sciences, ARD - Amsterdam Reproduction and Development, Center for Reproductive Medicine, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, Lee Kong Chian School of Medicine (LKCMedicine), Obstetrics and gynaecology |
| المصدر: | American Journal of Human Genetics The American journal of human genetics, Cell Press, 2018, Vol. 102, p. 116-132 American Journal of Human Genetics, Vol. 102, No 1 (2018) pp. 116-132 American journal of human genetics, vol. 102, no. 1, pp. 116-132 American journal of human genetics, 102(1), 116-132. Cell Press American Journal of Human Genetics, 102(1), 116. Cell Press DDD Study 2018, ' KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis ', American journal of human genetics, vol. 102, no. 1, pp. 116-132 . https://doi.org/10.1016/j.ajhg.2017.12.002 |
| بيانات النشر: | Elsevier, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Pathology, Microphthalmia, 0302 clinical medicine, Adolescent, Animals, Arthrogryposis/genetics, Brain/diagnostic imaging, Brain/embryology, Brain/pathology, Child, Female, Gene Knockdown Techniques, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Mutation/genetics, Pedigree, Proteins/genetics, Zebrafish, Zebrafish Proteins/genetics, arthrogryposis, brain malformations, cerebellar hypoplasia, clubfoot, hydrocephaly, whole-exome sequencing, Medicine, Missense mutation, Science::Medicine [DRNTU], ddc:576.5, Global developmental delay, Cerebellar hypoplasia, Genetics (clinical), Exome sequencing, Arthrogryposis, Hydrocephaly, Brain, Clubfoot, Whole-exome sequencing, medicine.symptom, medicine.medical_specialty, Article, 03 medical and health sciences, Dysgenesis, Genetics, Syndactyly, business.industry, Brain malformations, Proteins, Zebrafish Proteins, medicine.disease, 030104 developmental biology, Mutation, business, 030217 neurology & neurosurgery |
| الوصف: | Whole-exome and targeted sequencing of 13 individuals from 10 unrelated families with overlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allowing delineation of an autosomal-recessive multi-system syndrome, which we suggest to name Alkuraya-Kučinskas syndrome (MIM 617822). Shared phenotypic features representing the cardinal characteristics of this syndrome combine brain atrophy with clubfoot and arthrogryposis. Affected individuals present with cerebral parenchymal underdevelopment, ranging from major cerebral parenchymal thinning with lissencephalic aspect to moderate parenchymal rarefaction, severe to mild ventriculomegaly, cerebellar hypoplasia with brainstem dysgenesis, and cardiac and ophthalmologic anomalies, such as microphthalmia and cataract. Severe loss-of-function cases were incompatible with life, whereas those individuals with milder missense variants presented with severe global developmental delay, syndactyly of 2 nd and 3 rd toes, and severe muscle hypotonia resulting in incapacity to stand without support. Consistent with a causative role for KIAA1109 loss-of-function/hypomorphic variants in this syndrome, knockdowns of the zebrafish orthologous gene resulted in embryos with hydrocephaly and abnormally curved notochords and overall body shape, whereas published knockouts of the fruit fly and mouse orthologous genes resulted in lethality or severe neurological defects reminiscent of the probands' features. |
| وصف الملف: | application/pdf; image/pdf |
| اللغة: | English |
| تدمد: | 1537-6605 0002-9297 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c23a0c7a41844e5f0cd56648dd1d817 http://europepmc.org/articles/PMC5777449 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9c23a0c7a41844e5f0cd56648dd1d817 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376605 00029297 |
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