Identification of a Novel Pathogenic Variant in a Patient with a Neurodevelopmental Disorder

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2022 Apr 23

PMID 35456494

Authors

Gabriella Doddato

Alessandra Fabbiani

Valeria Scandurra

Roberto Canitano

Maria Antonietta Mencarelli

Alessandra Renieri

Francesca Ariani

Affiliations

Soon will be listed here.

Abstract

Genetic defects in the SHANK2 gene, encoding for synaptic scaffolding protein, are associated with a variety of neurodevelopmental conditions, including autism spectrum disorders and mild to moderate intellectual disability. Until now, limited patient clinical descriptions have been published. Only 13 unrelated patients with SHANK2 pathogenic variations or microdeletions have been reported worldwide. By Exome Sequencing, we identified a de novo stop-gain variant, c.334C>T, p.(Gln112*), in an Italian patient with a neurodevelopmental disorder. The patient (9 years old) presented the following facial features: a flat profile, thick eyebrows, long eyelashes, a bulbous nasal tip and a prominent columella, retracted ears, dental anomalies. The patient showed speech delay and mild neuromotor delay but not autism spectrum disorder. In conclusion, this patient with a novel pathogenic variant in SHANK2 enlarges the phenotypic spectrum of SHANK2-mutated patients and demonstrates that the severity of SHANK2-associated disorders is highly variable.

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