Heterozygous de novo variants in CSNK1G1 are associated with syndromic developmental delay and autism spectrum disorder,Clinical Genetics

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Heterozygous de novo variants in CSNK1G1 are associated with syndromic developmental delay and autism spectrum disorder
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-10-03 , DOI: 10.1111/cge.13851
Nina B Gold ₁ , Dong Li ₂ , Anna Chassevent ₃ , Frank J Kaiser ₄ , Ilaria Parenti ₄ , Tim M Strom _{5,

6} , Feliciano J Ramos ₇ , Beatriz Puisac ₇ , Juan Pié ₇ , Kirsty McWalter ₈ , Maria J Guillen Sacoto ₈ , Hong Cui ₈ , Reem Saadeh-Haddad ₉ , Constance Smith-Hicks ₁₀ , Lance Rodan ₁₁ , Edward Blair ₁₂ , Elizabeth Bhoj ₁₃

Affiliation

Division of Medical Genetics and Metabolism, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts, USA.
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Neurogenetics, The Kennedy Krieger Institute, Baltimore, Maryland, USA.
Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
Institute of Human Genetics, Technische Universität München, Munich, Germany.
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology and Department of Paediatrics, Hospital "Lozano Blesa", School of Medicine, University of Zaragoza, IIS-Aragón and CIBERER-GCV02, Zaragoza, Spain.
GeneDx Inc., Gaithersburg, Maryland, USA.
Division of Genetics, MedStar Georgetown University Hospital Department of Pediatrics, Washington, District of Columbia, USA.
Departments of Neurology and Neurogenetics, The Kennedy Krieger Institute, Baltimore, Maryland, USA.
Division of Genetics and Genomics and Division of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Oxford Centre for Genomic Medicine, ACE Building, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust, Oxford, UK.
Children's Hospital of Philadelphia, Division of Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

The gamma‐1 isoform of casein kinase 1, the protein encoded by CSNK1G1, is involved in the growth and morphogenesis of cells. This protein is expressed ubiquitously among many tissue types, including the brain, where it regulates the phosphorylation of N‐methyl‐D‐aspartate receptors and plays a role in synaptic transmission. One prior individual with a de novo variant in CSNK1G presenting with severe developmental delay and early‐onset epilepsy has been reported. Here we report an updated clinical history of this previously published case, as well as four additional individuals with de novo variants in CSNK1G1 identified via microarray‐based comparative genomic hybridization, exome, or genome sequencing. All individuals (n = 5) had developmental delay. At least three individuals had diagnoses of autism spectrum disorder. All participants were noted to have dysmorphic facial features, although the reported findings varied widely and therefore may not clearly be recognizable. None of the participants had additional major malformations. Taken together, our data suggest that CSNK1G1 may be a cause of syndromic developmental delay and possibly autism spectrum disorder.

中文翻译：

CSNK1G1 中的杂合子从头变异与综合征性发育迟缓和自闭症谱系障碍有关

酪蛋白激酶 1 的 gamma-1 亚型，由CSNK1G1编码的蛋白质，参与细胞的生长和形态发生。这种蛋白质在包括大脑在内的许多组织类型中普遍表达，在那里它调节 N-甲基-D-天冬氨酸受体的磷酸化并在突触传递中发挥作用。据报道，一名先前患有CSNK1G 新变体的个体出现严重的发育迟缓和早发性癫痫。在这里，我们报告了这个先前发表的病例的最新临床病史，以及另外四名在CSNK1G1 中具有从头变异的个体通过基于微阵列的比较基因组杂交、外显子组或基因组测序进行鉴定。所有个体（n = 5）都有发育迟缓。至少三个人被诊断为自闭症谱系障碍。所有参与者都被注意到有畸形的面部特征，尽管报告的结果差异很大，因此可能无法清楚地识别。没有一个参与者有额外的严重畸形。综上所述，我们的数据表明CSNK1G1可能是导致综合征性发育迟缓和自闭症谱系障碍的原因。

更新日期：2020-11-18

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