A novel missense variant in
epilepsy
platelet dense granules
serotonin
vesicular monoamine transporter 2
whole genome sequencing
Journal
JIMD reports
ISSN: 2192-8304
Titre abrégé: JIMD Rep
Pays: United States
ID NLM: 101568557
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
22
12
2018
accepted:
24
01
2019
entrez:
27
6
2019
pubmed:
27
6
2019
medline:
27
6
2019
Statut:
epublish
Résumé
Brain monoamine vesicular transport disease is an infantile onset neurodevelopmental disorder caused by variants in The presented case is of a child, born of healthy consanguineous parents, who exhibited hypotonia, mental disability, epilepsy, uncontrolled movements, and gastrointestinal problems. A trial treatment with L-DOPA proved unsuccessful and the exact neurological involvement could not be discerned due to normal metabolic and brain magnetic resonance imaging results.Platelet studies and whole genome sequencing were performed. At age 4, the child's platelets showed a mild aggregation and adenosine triphosphate secretion defect that could be explained by dysmorphic dense granules observed by electron microscopy. Interestingly, the dense granules were almost completely depleted of serotonin. A novel homozygous p.P316A missense variant in VMAT2 was detected in the patient and the consanguineous parents were found to be heterozygous for this variant. Although the presence of VMAT2 on platelet dense granules has been demonstrated before, this is the first report of defective platelet dense granule function related to absent serotonin storage in a patient with VMAT2 deficiency but without obvious clinical bleeding problems. This study illustrates the homology between serotonin metabolism in brain and platelets, suggesting that these blood cells can be model cells for some pathways relevant for neurological diseases. The literature on VMAT2 deficiency is reviewed.
Sections du résumé
BACKGROUND
BACKGROUND
Brain monoamine vesicular transport disease is an infantile onset neurodevelopmental disorder caused by variants in
CASE PRESENTATION
METHODS
The presented case is of a child, born of healthy consanguineous parents, who exhibited hypotonia, mental disability, epilepsy, uncontrolled movements, and gastrointestinal problems. A trial treatment with L-DOPA proved unsuccessful and the exact neurological involvement could not be discerned due to normal metabolic and brain magnetic resonance imaging results.Platelet studies and whole genome sequencing were performed. At age 4, the child's platelets showed a mild aggregation and adenosine triphosphate secretion defect that could be explained by dysmorphic dense granules observed by electron microscopy. Interestingly, the dense granules were almost completely depleted of serotonin. A novel homozygous p.P316A missense variant in VMAT2 was detected in the patient and the consanguineous parents were found to be heterozygous for this variant. Although the presence of VMAT2 on platelet dense granules has been demonstrated before, this is the first report of defective platelet dense granule function related to absent serotonin storage in a patient with VMAT2 deficiency but without obvious clinical bleeding problems.
CONCLUSIONS
CONCLUSIONS
This study illustrates the homology between serotonin metabolism in brain and platelets, suggesting that these blood cells can be model cells for some pathways relevant for neurological diseases. The literature on VMAT2 deficiency is reviewed.
Identifiants
pubmed: 31240161
doi: 10.1002/jmd2.12030
pii: JMD212030
pmc: PMC6498820
doi:
Types de publication
Case Reports
Langues
eng
Pagination
9-16Déclaration de conflit d'intérêts
Manisha Padmakumar, Jaak Jaeken, Vincent Ramaekers, Lieven Lagae, Daniel Greene, Chantal Thys, Chris Van Geet, NIHR BioResource, Kathleen Stirrups, Kate Downes, Ernest Turro, and Kathleen Freson declare that they have no conflict of interest.
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