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A novel nonsense variant in EXOC8 underlies a neurodevelopmental disorder
Human exocyst complex is an evolutionary conserved multimeric complex composed of proteins encoded by eight genes EXOC1-EXOC8 . It is known that the exocyst complex plays a role in ciliogenesis, cytokinesis, cell migration, autophagy, and fusion of secretory vesicles. Recently, loss of function vari...
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Published in: | Neurogenetics 2022-07, Vol.23 (3), p.203-212 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Human exocyst complex is an evolutionary conserved multimeric complex composed of proteins encoded by eight genes
EXOC1-EXOC8
. It is known that the exocyst complex plays a role in ciliogenesis, cytokinesis, cell migration, autophagy, and fusion of secretory vesicles. Recently, loss of function variants in
EXOC7
and
EXOC8
has been associated with abnormalities of cerebral cortical development leading to a neurodevelopmental phenotype. Neurodevelopmental disorders are a huge group of clinically and genetically heterogeneous disorders. In the present study, we recruited a large consanguineous family segregating a neurodevelopmental disorder in an autosomal recessive form. We performed clinical phenotyping by imaging the patient’s brain followed by whole exome sequencing examining DNA from two affected individuals. The clinical phenotypes of the disease were suggestive of brain atrophy. Clinical examination revealed intellectual impairment with hypertonia and brisk reflexes. WES followed by Sanger sequencing revealed a novel homozygous nonsense mutation [
EXOC8
; NM_175876.5; c.1714G > T; p.(Glu572Ter)] in the DNA of affected individuals. Both parents of the patients were heterozygous for the identified mutation. All the pathogenicity prediction softwares predicted the identified variant as disease causing. This study reports a second protein-truncating variant in
EXOC8
. The findings confirm that loss of function variants in
EXOC8
underlies a neurodevelopmental disorder. The identification of a protein-truncating variant in
EXOC8
in the current study can be helpful in establishing genotype–phenotype correlations. Our results also provide new insights into genetic counseling and clinical management for the affected individuals. |
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ISSN: | 1364-6753 1364-6745 1364-6753 |
DOI: | 10.1007/s10048-022-00692-7 |