دورية أكاديمية
أعرض في EDS

De Novo GLI3 Pathogenic Variants May Cause Hypotonia and a Range of Brain Malformations Without Skeletal Abnormalities.

التفاصيل البيبلوغرافية
العنوان: De Novo GLI3 Pathogenic Variants May Cause Hypotonia and a Range of Brain Malformations Without Skeletal Abnormalities.
المؤلفون: Siafa L; Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Argilli E; Departments of Neurology and Pediatrics, Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California., Sherr EH; Departments of Neurology and Pediatrics, Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California., Myers KA; Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Division of Child Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada; Department of Neurology & Neurosurgery, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada. Electronic address: kenneth.myers@mcgill.ca.
المصدر: Pediatric neurology [Pediatr Neurol] 2022 Jun; Vol. 131, pp. 1-3. Date of Electronic Publication: 2022 Mar 31.
نوع المنشور: Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Publishing Country of Publication: United States NLM ID: 8508183 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5150 (Electronic) Linking ISSN: 08878994 NLM ISO Abbreviation: Pediatr Neurol Subsets: MEDLINE
أسماء مطبوعة: Publication: New York Ny : Elsevier Science Publishing
Original Publication: Chippewa Falls, Wis. : Professional Publications, [c1985-
مواضيع طبية MeSH: Malformations of Cortical Development*/complications , Polydactyly*/complications , Polydactyly*/diagnostic imaging , Polydactyly*/genetics, Brain/diagnostic imaging ; Brain/pathology ; Child, Preschool ; Hedgehog Proteins/genetics ; Humans ; Male ; Muscle Hypotonia/complications ; Muscle Hypotonia/genetics ; Nerve Tissue Proteins/genetics ; Phenotype ; Syndrome ; Zinc Finger Protein Gli3/genetics
مستخلص: Background: GLI3 encodes a zinc finger transcription factor that plays a role in the sonic hedgehog pathway. Germline pathogenic GLI3 variants are associated with Greig cephalopolysyndactyly and Pallister-Hall syndromes, two syndromes involving brain malformation and polydactyly.
Methods: We identified patients with pathogenic GLI3 variants and brain malformations in the absence of polydactyly or other skeletal malformation.
Results: Two patients were identified. Patient #1 is a 4-year-old boy with hypotonia and global developmental delay. Brain MRI showed a focal cortical dysplasia, but he had no history of seizures. Genetic testing identified a de novo likely pathogenic GLI3 variant: c.4453A>T, p.Asn1485Tyr. Patient #2 is a 4-year-old boy with hypotonia, macrocephaly, and global developmental delay. His brain MRI showed partial agenesis of the corpus callosum, dilatation of the right lateral ventricle, and absent hippocampal commissure. Genetic testing identified a de novo pathogenic GLI3 variant: c.4236_4237del, p.Gln1414AspfsTer21. Neither patient had polydactyly or any apparent skeletal abnormality.
Conclusions: These patients widen the spectrum of clinical features that may be associated with GLI3 pathogenic variants to include hypotonia, focal cortical dysplasia, and other brain malformations, in the absence of apparent skeletal malformation. Further study is needed to determine if GLI3 pathogenic variants are a more common cause of focal cortical dysplasia or corpus callosum agenesis than presently recognized.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 HG009141 United States HG NHGRI NIH HHS; R01 NS058721 United States NS NINDS NIH HHS; UM1 HG008900 United States HG NHGRI NIH HHS
فهرسة مساهمة: Keywords: Agenesis of corpus callosum; Focal cortical dysplasia; GLI3; Hypotonia; Macrocephaly
المشرفين على المادة: 0 (GLI3 protein, human)
0 (Hedgehog Proteins)
0 (Nerve Tissue Proteins)
0 (Zinc Finger Protein Gli3)
تواريخ الأحداث: Date Created: 20220418 Date Completed: 20220525 Latest Revision: 20240607
رمز التحديث: 20240607
مُعرف محوري في PubMed: PMC10257559
DOI: 10.1016/j.pediatrneurol.2022.03.005
PMID: 35436645
قاعدة البيانات: MEDLINE
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