Female patient with autistic disorder, intellectual disability, and co‐morbid anxiety disorder: Expanding the phenotype associated with the recurrent 3q13.2–q13.31 microdeletion

Abstract

In recent years, the advent of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays and its use as a first genetic test for the diagnosis of patients with neurodevelopmental phenotypes has allowed the identification of novel submicroscopic chromosomal abnormalities (namely, copy number variants or CNVs), imperceptible by conventional cytogenetic techniques. The 3q13.31 microdeletion syndrome (OMIM #615433) has been defined as a genomic disorder mainly characterized by developmental delay, postnatal overgrowth, hypotonia, genital abnormalities in males, and characteristic craniofacial features. Although the 3q13.31 CNVs are variable in size, a 3.4 Mb recurrently altered region at 3q13.2-q13.31 has been recently described and non-allelic homologous recombination (NAHR) mediated by flanking human endogenous retrovirus (HERV-H) elements has been suggested as the mechanism of deletion formation. We expand the phenotypic spectrum associated with this recurrent deletion performing the clinical description of a 9-year-old female patient with autistic disorder, total absence of language, intellectual disability, anxiety disorder and disruptive, and compulsive eating behaviors. The array-based molecular karyotyping allowed the identification of a de novo recurrent 3q13.2-q13.31 deletion encompassing 25 genes. In addition, we compare her clinical phenotype with previous reports of patients with neurodevelopmental and behavioral disorders and proximal 3q microdeletions. Finally, we also review the candidate genes proposed so far for these phenotypes.

Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families

“…For instance, SUMF1 40 , HSPBP1 41 , TRIM9 42 , DUSP3 24 and BOC 43 . WES detected de novo variants in three genes (Table 2).…”

“…In our study, 32 of the detected variants were observed in genes previously reported in ASD (either in Autism databases or in literature) (Table 1 ). For instance, SUMF1 40 , HSPBP1 41 , TRIM9 42 , DUSP3 24 and BOC 43 . WES detected de novo variants in three genes (Table 2 ).…”

An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development

“…All nine individuals variably express cognitive delays and abnormal behavior, and three of them are diagnosed with ASD [ 77 ]. An independent study reported another case about a patient with ASD carrying the same microdeletion [ 78 ]. Therefore, this clinical evidence supports our hypothesis that active ERV associated with retrotransposition can disperse ERV copies throughout the genome and increase the chance of CNV formation in the two BTBR strains.…”