Neurodevelopmental disorders are a group involving developmental impairments of the central nervous system. These include intellectual disability (ID), autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), impaired motor function, learning, language or non-verbal communication and tics [1]. Epidemiological studies have identified various risk factors for neurodevelopmental disorders. Submicroscopic chromosomal copy-number variants (CNVs) are some of the contributing factors. Because of the large genetic heterogeneity of neurodevelopmental disorders, high-resolution whole-genome analyses, such as array comparative genomic hybridization (aCGH), are useful tools to study the etiopathogenesis of these disorders and therefore aCGH is recommended as a first-tier clinical diagnostic test for patients with NI and ASDs [2]. Moreover, the advent of aCGH technologies has paved the way to the discovery of novel genes. We have identified and characterized a novel microdeletion in the 20q13.11q13.12 region in a boy with emotional and behavioral problems, movement stereotypes, tics and attention deficit disorder; we further report on associated clinical and neurological findings in the patient.
The patient was born to non-consanguineous parents at 40 Hbd weeks of gestation by caesarean section. Body parameters were within the normal range with birth weight of 3250 g, body length 58 cm and head circumference 34 cm. Early developmental milestones were normally attained. At school age (from age 6) he was noted to have stereotyped movements, nervous tics, social and emotional disturbances, and attention deficit disorder. Currently – at age 13 − he still manifests nervous tics in stressful situations. He has been diagnosed with dyslexia, dysgraphia, attention deficit disorder and continues to have learning difficulties. His intelligence is assessed at average level. No significant dysmorphic characteristics have been observed aside from a slightly asymmetric and narrow chest, small ears, and synophrys. EEG analysis showed discrete changes on the right temporal area. The family history is positive for Asperger syndrome in his father’s brother, depression in his mother and schizophrenia in his paternal grandmother.
Oligonucleotide array comparative genomic hybridization (aCGH) was performed using 8x60K from Oxford Gene Technology (CytoSure ISCA v2). Array CGH has genome-wide coverage with an average resolution of 120 kb. DNA digestion, labeling, and hybridization were performed following the manufacturer’s instructions.
The interstitial deletion of 424 kb was identified at chromosome 20q13.11q13.12 using aCGH (43,117,849-43,541,875 - UCSC Genome Browser on Human Dec 2013 GRCh38/hg38). The deleted region contained three genes:
Array CGH analysis in our patient showing an 424 kb deletion in chromosome 20q13.11q13.12. Two genes are deleted:
Ryc. 1. W badaniu metodą aCGH u naszego pacjenta stwierdzono delecję regionu 20q13.11q13.12 o wielkości 424 kb. Delecji uległy dwa geny: SFRS6 , L3MBTL oraz pierwszy ekson genu PTPRT.
We performed a literature review and database search for individuals carrying a microdeletion involving the long arm of chromosome 20. To date, there are very few medical reports of 20q13 deletion, most of which involve regions more distal to our case [3, 4, 5]. We present, to our knowledge, the first case of 20q13.11q13.12 microdeletion encompassing the
The deleted region observed in our patient includes three genes:
A large group of the genes identified as risk factors for ASD plays an important role in synaptic homeostasis [9]. This indicates that disturbances of synaptic homeostasis are likely associated with ASD pathogenesis. PTPRT is a candidate protein for modulating proteins that play an important role in synaptic transmission and synapse formation. Rajamani et al. generated a knocking mouse line model of the
The second gene deleted in our patient is
The
In summary, the established function of the