Enhancing DLG2 Implications in Neuropsychiatric Disorders: Analysis of a Cohort of Eight Patients with 11q14.1 Imbalances

Veronica Bertini; Roberta Milone; Paola Cristofani; Francesca Cambi; Chiara Bosetti; Filippo Barbieri; Silvano Bertelloni; Giovanni Cioni; Angelo Valetto; Roberta Battini

doi:10.3390/genes13050859

Enhancing DLG2 Implications in Neuropsychiatric Disorders: Analysis of a Cohort of Eight Patients with 11q14.1 Imbalances

Genes (Basel). 2022 May 12;13(5):859. doi: 10.3390/genes13050859.

Authors

Affiliations

¹ Cytogenetic Unit, Department of Laboratory Medicine, Azienda Ospedaliero-Univeristaria Pisana, Via Roma 57, 56100 Pisa, Italy.
² Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, 56125 Pisa, Italy.
³ Mental Health Department, ASL Toscana Nordovest, 56100 Pisa, Italy.
⁴ Pediatric Endocrinology, Department of Obstetrics, Gynecology and Pediatrics, Azienda Ospedaliero-Universitaria Pisana, Via Roma 57, 56100 Pisa, Italy.
⁵ Department of Clinical and Experimental Medicine, University of Pisa, 56100 Pisa, Italy.

Abstract

Neurodevelopmental disorders (NDDs) are considered synaptopathies, as they are due to anomalies in neuronal connectivity during development. DLG2 is a gene involved insynaptic function; the phenotypic effect of itsalterations in NDDs has been underestimated since few cases have been thoroughly described.We report on eight patients with 11q14.1 imbalances involving DLG2, underlining its potential effects on clinical presentation and its contribution to NDD comorbidity by accurate neuropsychiatric data collection. DLG2 is a very large gene in 11q14.1, extending over 2.172 Mb, with alternative splicing that gives rise to numerous isoforms differentially expressed in brain tissues. A thorough bioinformatic analysis of the altered transcripts was conducted for each patient. The different expression profiles of the isoforms of this gene and their influence on the excitatory-inhibitory balance in crucial brain structures could contribute to the phenotypic variability related to DLG2 alterations. Further studies on patients would be helpful to enrich clinical and neurodevelopmental findings and elucidate the molecular mechanisms subtended to NDDs.

Keywords: ADHD; array-CGH; autism spectrum disorder; intellectual disability; neurodevelopmental disorders; protein-coding transcripts.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing
Chromosome Structures
Chromosomes, Human, Pair 11* / genetics
Guanylate Kinases* / genetics
Humans
Neurodevelopmental Disorders* / genetics
Protein Isoforms / genetics
Tumor Suppressor Proteins* / genetics

Substances

Protein Isoforms
Tumor Suppressor Proteins
DLG2 protein, human
Guanylate Kinases

Grants and funding

This work belongs to the project “Study on phenotype–genotype correlations of genetic rare diseases expressing in developmental age with neuropsychiatric symptoms” funded by the “Sarzana Family Donation”. Furthermore, it was partially supported by the Italian Ministry of Health (Grant-RC2021) and taxpayer contributions (‘5 × 1000’) to the IRCCS Stella Maris Foundation for the year 2021 (RB, RM).