KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis.

Autor:	Gueneau L; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland., Fish RJ; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland., Shamseldin HE; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia., Voisin N; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland., Tran Mau-Them F; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM Unité 964, 67404 Illkirch Cedex, France; Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France., Preiksaitiene E; Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania., Monroe GR; Department of Genetics and Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Lai A; KK Women's and Children's Hospital, Singapore 229899, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University-Imperial College London, Singapore 639798, Singapore., Putoux A; Service de Génétique, Hospices Civils de Lyon, 69002 Lyon, France; Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, 69675 Bron Cedex, France., Allias F; Département de Pathologie, Hospices Civils de Lyon, 69002 Lyon, France., Ambusaidi Q; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia., Ambrozaityte L; Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania., Cimbalistienė L; Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania., Delafontaine J; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., Guex N; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., Hashem M; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia., Kurdi W; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia., Jamuar SS; KK Women's and Children's Hospital, Singapore 229899, Singapore; Duke-NUS Medical School, Singapore 169857, Singapore., Ying LJ; KK Women's and Children's Hospital, Singapore 229899, Singapore., Bonnard C; Institute of Medical Biology, A(∗)STAR, Singapore 138648, Singapore., Pippucci T; Sant'Orsola-Malpighi Hospital, Medical Genetics Unit, Pavillon 11, 2nd floor, Via Massarenti 9, 40138 Bologna, Italy., Pradervand S; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., Roechert B; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., van Hasselt PM; Department of Genetics and Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Wiederkehr M; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland., Wright CF; Deciphering Developmental Disorders (DDD) Study, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Xenarios I; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., van Haaften G; Department of Genetics and Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Shaw-Smith C; Department of Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter EX1 2ED, UK., Schindewolf EM; Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Neerman-Arbez M; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland., Sanlaville D; Service de Génétique, Hospices Civils de Lyon, 69002 Lyon, France; Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, 69675 Bron Cedex, France., Lesca G; Service de Génétique, Hospices Civils de Lyon, 69002 Lyon, France; Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, 69675 Bron Cedex, France., Guibaud L; Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, 69675 Bron Cedex, France; Département d'imagerie pédiatrique et fœtale, Centre Pluridisciplinaire de Diagnostic Prénatal, Hôpital Femme Mère Enfant, Université Claude Bernard Lyon 1, 69677 Bron Cedex, France., Reversade B; Institute of Medical Biology, A(∗)STAR, Singapore 138648, Singapore; Institute of Molecular and Cell Biology (IMCB), A(∗)STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Singapore 138673, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Amsterdam Reproduction & Development, Academic Medical Centre & VU University Medical Center, 1105 AZ Amsterdam, the Netherlands., Chelly J; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM Unité 964, 67404 Illkirch Cedex, France; Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France., Kučinskas V; Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania., Alkuraya FS; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh 12371, Saudi Arabia. Electronic address: falkuraya@kfshrc.edu.sa., Reymond A; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: alexandre.reymond@unil.ch.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2018 Jan 04; Vol. 102 (1), pp. 116-132. Date of Electronic Publication: 2017 Dec 28.
DOI:	10.1016/j.ajhg.2017.12.002
Abstrakt:	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. (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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