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12q13.12q13.13 microdeletion encompassing ACVRL1 and SCN8A genes: Clinical report of a new contiguous gene syndrome.

Authors
  • Poisson, Alice1
  • Lesca, Gaetan2
  • Chatron, Nicolas2
  • Favre, Emilie3
  • Cottin, Vincent4
  • Gamondes, Delphine5
  • Sanlaville, Damien2
  • Edery, Patrick6
  • Giraud, Sophie7
  • Demily, Caroline8
  • Dupuis-Girod, Sophie7
  • 1 GénoPsy, Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier, Lyon, France; Lyon Neuroscience Research Centre, CNRS UMR5292, INSERM U1028, Lyon 2, France. Electronic address: [email protected] , (France)
  • 2 Hospices Civils de Lyon, Genetic Department and Molecular Biology Laboratory, Centre de Biologie Est, Bron, F-69677, France; Université Claude Bernard Lyon 1, F-69100, Villeurbanne, France. , (France)
  • 3 GénoPsy, Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier, Lyon, France; Lyon Neuroscience Research Centre, CNRS UMR5292, INSERM U1028, Lyon 2, France. , (France)
  • 4 Hospices Civils de Lyon, Department of Pulmonary Medicine and National Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Bron, F-69677, France; Université Claude Bernard Lyon 1, F-69100, Villeurbanne, France. , (France)
  • 5 Hospices Civils de Lyon, Department of Radiology, Louis Pradel Hospital, Bron, F-69677, France. , (France)
  • 6 Hospices Civils de Lyon, Genetic Department and National HHT Reference Center, Femme-Mère-Enfants Hospital, Bron, F-69677, France; Université Claude Bernard Lyon 1, F-69100, Villeurbanne, France. , (France)
  • 7 Hospices Civils de Lyon, Genetic Department and National HHT Reference Center, Femme-Mère-Enfants Hospital, Bron, F-69677, France. , (France)
  • 8 GénoPsy, Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier, Lyon, France; Lyon Neuroscience Research Centre, CNRS UMR5292, INSERM U1028, Lyon 2, France; Université Claude Bernard Lyon 1, F-69100, Villeurbanne, France. , (France)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Nov 01, 2019
Volume
62
Issue
11
Pages
103565–103565
Identifiers
DOI: 10.1016/j.ejmg.2018.10.017
PMID: 30389587
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Hereditary hemorrhagic telangiectasia is usually linked to the presence of a pathogenic mutation ACVRL1 or ENG. Thus, apparently there is no benefit to perform an array CGH in case of HHT. However, ENG has been involved in a contiguous gene syndrome due to a de novo 9q33.3q34.11 microdeletion. We describe here a new contiguous gene syndrome involving ACVRL1 gene. A 50-year-old female patient had a typical clinical presentation of hereditary hemorrhagic telangiectasia (HHT) with epistaxis, cutaneous-mucous telangiectases, arteriovenous malformation. She also presented a cognitive disability. Cognitive assessment showed a heterogeneous cognitive disorder predominating in the executive sphere without intellectual deficiency. She had no peculiar morphological feature. Neurological examination disclosed the presence of contralateral mirror movements during voluntary movement of each hand. A heterozygous deletion of the whole ACVRL1 gene (exons 1 to 10) was found to be responsible for the HHT features. To investigate further the dysexecutive syndrome and the mirror movements, we performed oligonucleotide array comparative genomic hybridization (array CGH) study (180K, Agilent, Santa-Clara, CA, USA). This study revealed a de novo 1.58 Mb deletion on chromosome 12q13.12q13.13 encompassing the ACVRL1 and SCN8A genes. To our knowledge, this deletion has not been previously reported and defines a new contiguous gene syndrome. The loss of one ACVRL1 allele is likely to be responsible for the HHT phenotype, while the deletion of the SCN8A gene is likely to be the cause of the mild cognitive disorder. SCN8A haploinsufficiency might also be involved in the occurrence of mirror movements. This report highlights the benefit of searching for large rearrangements in cases including unusual symptoms in association with HHT. On the other hand, an early diagnosis of 12q13.12q13.13 microdeletion based on the presence of a dysexecutive syndrome and/or mirror movement may allow to prevent HHT complications. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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