A novel microduplication in INPP5A segregates with schizophrenia spectrum disorder in the family of a patient with both childhood onset schizophrenia and autism spectrum disorder

Autor: Małgorzata Drozd, Maria Capovilla, Florence Askenazy, Susanne Thümmler, Arnaud Fernandez, Barbara Bardoni
Přispěvatelé: Hôpitaux Pédiatriques de Nice Lenval (CHU-Lenval), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
Rok vydání: 2021
Předmět:
0301 basic medicine
inositol pathway
INPP5A
MESH: Pedigree
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
CNV
Central nervous system
Dendritic spine morphogenesis
030105 genetics & heredity
MESH: Phenotype
behavioral disciplines and activities
MESH: Child Development Disorders
Pervasive
MESH: Brain
03 medical and health sciences
Neurodevelopmental disorder
MESH: Child
mental disorders
Gene duplication
Genetics
medicine
MESH: Animals
childhood-onset schizophrenia
MESH: Inositol Polyphosphate 5-Phosphatases
MESH: Mice
Gene
Genetics (clinical)
MESH: Adolescent
MESH: Autism Spectrum Disorder
MESH: Humans
business.industry
MESH: Genetic Predisposition to Disease
[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
MESH: Adult
medicine.disease
neurodevelopmental disorder
MESH: Male
Pathophysiology
MESH: Siblings
030104 developmental biology
medicine.anatomical_structure
MESH: Young Adult
Autism spectrum disorder
Schizophrenia
MESH: Disease Models
Animal
business
MESH: Female
MESH: Schizophrenia
Childhood
Zdroj: American Journal of Medical Genetics Part A
American Journal of Medical Genetics Part A, Wiley, 2021, 185 (6), pp.1841-1847. ⟨10.1002/ajmg.a.62155⟩
ISSN: 1552-4833
1552-4825
DOI: 10.1002/ajmg.a.62155
Popis: Childhood-Onset Schizophrenia (COS) is a very rare and severe psychiatric disorder defined by adult schizophrenia symptoms occurring before the age of 13. We report a microduplication in the 10q26.3 region including part of the Inositol Polyphosphate-5-Phosphatase A (INPP5A) gene that segregates with Schizophrenia Spectrum Disorders (SSDs) in the family of a female patient affected by both COS and Autism Spectrum Disorder (ASD). Phenotyping and genotyping (including CGH-array) were performed for mother, healthy sister, and affected child according to the GenAuDiss protocol (NCT02565524). The duplication size is 324 kb and is present in a patient with COS and in her mother with SSD, but not in the patient's healthy sister. INPP5A encodes a membrane-associated 43 kDa type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. This protein is found both in mouse and human brains and we found that its Drosophila homologue 5PtaseI is specifically expressed in the central nervous system. Hydrolyzed products from InsP3 5-phosphatases mobilize intracellular calcium, which is relevant for dendritic spine morphogenesis in neurons and altered in both schizophrenia and ASD. These may constitute arguments in favor of this gene alteration in the pathophysiology of COS.
Databáze: OpenAIRE
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