Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathy
Abstract Background The epileptic encephalopathies display extensive locus and allelic heterogeneity. Biallelic truncating DOCK7 variants were recently reported in five children with early‐onset epilepsy, intellectual disability, and cortical blindness, indicating that DOCK7 deficiency causes a spec...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-03-01
|
Series: | Molecular Genetics & Genomic Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1002/mgg3.1607 |
id |
doaj-7bd40df55dd6455398cd4c6b13bd02b3 |
---|---|
record_format |
Article |
spelling |
doaj-7bd40df55dd6455398cd4c6b13bd02b32021-08-21T11:45:29ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-03-0193n/an/a10.1002/mgg3.1607Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathyEdda Haberlandt0Taras Valovka1Tanja Janjic2Thomas Müller3Georgios Blatsios4Daniela Karall5Andreas R. Janecke6Department of Pediatrics I Medical University of Innsbruck Innsbruck AustriaDepartment of Pediatrics I Medical University of Innsbruck Innsbruck AustriaDepartment of Neuroradiology Medical University of Innsbruck Innsbruck AustriaDepartment of Pediatrics I Medical University of Innsbruck Innsbruck AustriaDepartment of Ophthalmology Medical University of Innsbruck Innsbruck AustriaDepartment of Pediatrics I Medical University of Innsbruck Innsbruck AustriaDepartment of Pediatrics I Medical University of Innsbruck Innsbruck AustriaAbstract Background The epileptic encephalopathies display extensive locus and allelic heterogeneity. Biallelic truncating DOCK7 variants were recently reported in five children with early‐onset epilepsy, intellectual disability, and cortical blindness, indicating that DOCK7 deficiency causes a specific type of epileptic encephalopathy. Methods We identified 23‐ and 27‐year‐old siblings with the clinical pattern reported for DOCK7 deficiency, and conducted genome‐wide linkage analysis and WES. The consequences of a DOCK7 variant were analyzed on the transcript and protein level in patients’ fibroblasts. Results We identified a novel homozygous DOCK7 frameshift variant, an intragenic tandem duplication of 124‐kb, previously missed by CGH array, in adult patients. Patients display atrophy in the occipital lobe and pontine hypoplasia with marked pontobulbar sulcus, and focal atrophy of occasional cerebellar folia is a novel finding. Recognizable dysmorphic features include normo‐brachycephaly, narrow forehead, low anterior and posterior hairlines, prominent ears, full cheeks, and long eyelashes. Our patients function on the level of 4‐year‐old children, never showed signs of regression, and seizures are largely controlled with multi‐pharmacotherapy. Studies of patients’ fibroblasts showed nonsense‐mediated RNA decay and lack of DOCK7 protein. Conclusion DOCK7 deficiency causes a definable clinical entity, a recognizable type of epileptic encephalopathy.https://doi.org/10.1002/mgg3.1607cortical blindnessDOCK7epileptic encephalopathynonsense‐mediated RNA decayrecognizable syndrome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Edda Haberlandt Taras Valovka Tanja Janjic Thomas Müller Georgios Blatsios Daniela Karall Andreas R. Janecke |
spellingShingle |
Edda Haberlandt Taras Valovka Tanja Janjic Thomas Müller Georgios Blatsios Daniela Karall Andreas R. Janecke Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathy Molecular Genetics & Genomic Medicine cortical blindness DOCK7 epileptic encephalopathy nonsense‐mediated RNA decay recognizable syndrome |
author_facet |
Edda Haberlandt Taras Valovka Tanja Janjic Thomas Müller Georgios Blatsios Daniela Karall Andreas R. Janecke |
author_sort |
Edda Haberlandt |
title |
Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathy |
title_short |
Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathy |
title_full |
Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathy |
title_fullStr |
Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathy |
title_full_unstemmed |
Characteristic facial features and cortical blindness distinguish the DOCK7‐related epileptic encephalopathy |
title_sort |
characteristic facial features and cortical blindness distinguish the dock7‐related epileptic encephalopathy |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2021-03-01 |
description |
Abstract Background The epileptic encephalopathies display extensive locus and allelic heterogeneity. Biallelic truncating DOCK7 variants were recently reported in five children with early‐onset epilepsy, intellectual disability, and cortical blindness, indicating that DOCK7 deficiency causes a specific type of epileptic encephalopathy. Methods We identified 23‐ and 27‐year‐old siblings with the clinical pattern reported for DOCK7 deficiency, and conducted genome‐wide linkage analysis and WES. The consequences of a DOCK7 variant were analyzed on the transcript and protein level in patients’ fibroblasts. Results We identified a novel homozygous DOCK7 frameshift variant, an intragenic tandem duplication of 124‐kb, previously missed by CGH array, in adult patients. Patients display atrophy in the occipital lobe and pontine hypoplasia with marked pontobulbar sulcus, and focal atrophy of occasional cerebellar folia is a novel finding. Recognizable dysmorphic features include normo‐brachycephaly, narrow forehead, low anterior and posterior hairlines, prominent ears, full cheeks, and long eyelashes. Our patients function on the level of 4‐year‐old children, never showed signs of regression, and seizures are largely controlled with multi‐pharmacotherapy. Studies of patients’ fibroblasts showed nonsense‐mediated RNA decay and lack of DOCK7 protein. Conclusion DOCK7 deficiency causes a definable clinical entity, a recognizable type of epileptic encephalopathy. |
topic |
cortical blindness DOCK7 epileptic encephalopathy nonsense‐mediated RNA decay recognizable syndrome |
url |
https://doi.org/10.1002/mgg3.1607 |
work_keys_str_mv |
AT eddahaberlandt characteristicfacialfeaturesandcorticalblindnessdistinguishthedock7relatedepilepticencephalopathy AT tarasvalovka characteristicfacialfeaturesandcorticalblindnessdistinguishthedock7relatedepilepticencephalopathy AT tanjajanjic characteristicfacialfeaturesandcorticalblindnessdistinguishthedock7relatedepilepticencephalopathy AT thomasmuller characteristicfacialfeaturesandcorticalblindnessdistinguishthedock7relatedepilepticencephalopathy AT georgiosblatsios characteristicfacialfeaturesandcorticalblindnessdistinguishthedock7relatedepilepticencephalopathy AT danielakarall characteristicfacialfeaturesandcorticalblindnessdistinguishthedock7relatedepilepticencephalopathy AT andreasrjanecke characteristicfacialfeaturesandcorticalblindnessdistinguishthedock7relatedepilepticencephalopathy |
_version_ |
1721200590568030208 |