Original article
17q23.3 de novo microdeletion involving only TANC2 gene: A new case

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Abstract

Neurodevelopmental disorders (NDDs) show a wide range of overlapping clinical features. Intellectual disability (ID), developmental delay (DD), autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), language and communication disorders with or without motor abnormalities and/or epilepsy have been reported associated to single or multiple genes but in many cases the genetic basis remains unknown.

The increasingly use of array-CGH has significantly improved the yield of diagnosing genomic disorders and led to the identification of several novel microdeletion and microduplication syndromes.

TANC2 encodes a synaptic scaffold protein interacting with multiple neuropsychiatric disorder-related postsynaptic density (PSD) proteins in dendrites.

Here, we describe a new case of TANC2 gene disruption in a 17q23.3 de novo microdeletion identified by array-CGH. The patient presented craniofacial dysmorphic features, hypotonia, and severe cognitive and motor impairment.

In conclusion, our data add a further line of evidence supporting the role of TANC2 in NDDs and will help further researches to elucidate the regulatory mechanism of synaptic function and plasticity related to TANC2 haploinsufficiency.

Introduction

Neurodevelopmental disorders (NDDs) show a wide range of overlapping clinical features associated to single or multiple genes but in many cases, the genetic basis remains unknown (American Psychiatric Association, 2013).

Recently, 20 individuals with disruptive mutations and microdeletions in TANC2 have been reported (Guo et al., 2019). TANC2 (OMIM 615047; tetratricopeptide repeat-, ankyrin repeat-, and coiled-coil-containing protein 2) regulates dendritic spines and excitatory synapses. Particularly, TANC2 together with CaM and liprin-a regulates KIF1A-dependent transport that is responsible for axonal transporter of synaptic vesicles (Han et al., 2010; Stucchi et al., 2018).

The neurodevelopmental phenotype reported in patients with TANC2 pathogenetic variants is characterized by autism spectrum disorders (ASD), intellectual disability (ID), speech and motor delay, facial dysmorphisms, epilepsy, a pattern of complex behavioural dysfunctions and other features such as chronic constipation, ataxia, deformity of spine or chest, and strabismus. Individuals most severely affected show features similar to a Rett-like phenotype (Guo et al., 2019).

Here, we describe a new case of TANC2 gene disruption in 17q23.3 microdeletion identified by array-CGH. The patient presented craniofacial dysmorphic features, hypotonia, profound ID.

Section snippets

Clinical report

The patient is the only child to healthy, non-consanguineous Italian parents. Family history revealed, from paternal side, a first degree uncle affected by sarcoma who died at the age of 24 years, the paternal grandmother with a no better specified cerebral cancer and a second degree uncle died by kidney cancer at the age of 50.

He was born at 40 weeks of gestation following a pregnancy remarkable for the ultrasound finding of pulmonary stenosis, after a previous miscarriage. Karyotype on

Material and methods

Array-CGH was performed on DNA sample, extracted from the patient's peripheral blood and their parents according to standard methods, using a whole-genome 180 K Agilent array with ~13 Kb overall median probe spacing (Human Genome CGH Microarray, Agilent Technologies, Santa Clara, CA, USA), according to the manufacturer's protocol. Data were analysed using Agilent Cytogenomics 4.0.3.12. All genomic positions were reported according to the human genome assembly (GRCh37/hg19).

Results

Array-CGH analysis of the patient showed an interstitial deletion of the long arm of chromosome 17. The deleted 17q23.3 region (186.224 bp) spanned from nucleotide 61,167,025 bp (oligomer A _16P03273296) (first deleted) to nucleotide 61,353,248 bp (oligomer A_16P20699236) (last deleted) disrupting exons 3–7 of the TANC2 gene and resulted de novo (Fig. 2) (ClinVar accession number: SCV001431009 http://www.ncbi.nlm.nih.gov/clinvar). However, we cannot exclude the presence of a cryptic mosaic in

Discussion

TANC2 encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing) family that includes TANC1 and TANC2. Specifically, TANC2 is a synaptic scaffold protein that interacts and co-localizes with multiple postsynaptic-density proteins in dendrites in various brain regions to regulate dendritic spines and excitatory synapse formation.

During rat brain development, Tanc2 expression is detectable at embryonic stages and persists postnatally, albeit with reduced

Consent

Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Funding

This work was supported by “Cinque per mille dell’IRPEF-Finanziamento della ricerca sanitaria” and “Finanziamento Ricerca Corrente, Ministero Salute (contributo per la ricerca intramurale).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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