Abstract

Background: In the last decades, it has been possible to identify thousands of genes or gene loci implicated in the etiology of syndromic autism spectrum disorders. Those genes play an important role in neuronal migration, extension, branching of the neurites, synaptic function, transcriptional regulation and construction of neuronal network. AUTS2 gene, also named as the “activator of transcription and developmental regulator”, has been associated with a syndromic autism disorder named “AUTS2 syndrome” characterised by intelectual disability, autistic features, and mild dysmorphic characteristics. Since the first description of AUTS2 syndrome, there have been reported more than 60 cases, most of them from western countries. Our aim is to present the first case of a Mexican boy with AUTS2 syndrome and a novel pathogenic mutation of AUTS2 gene.

Methods: The proband is a 7-year 2-month-old Mexican boy, with growth and global developmental delay, dysmorphic features, such as, high broad forehead, highly arched and broad eyebrows, telecanthus, epicanthic fold, anteverted nares, upturned and short philtrum, high arch palate, small mouth, abnormal teeth, mild micro-retrognathia, low-set and cupped left ear, and camptodactily of the fifth rigth finger.

Results: A cytogenetic analysis revealed a normal male karyotype of 46,XY. In order to detect copy number aberrations, a Microarray-based comparative genomic hybridization analysis was conducted. A pathogenic heterozygous CNV was identified in 7q11.2 involving exons 7–17 at the C-terminal of AUTS2 gene. The assesment of autism was permormed applying the specific tests ADI-R and ADOS-G concluding that the patient meets criteria for ASD.

Conclusions: The phenotype of the present case corresponds to a severe syndrome according to the AUTS2 syndrome severity score, which correlates to genotype characterized by an intragenic deletion between exons 7 and 17 which affects the short AUTS2 isoform. Therefore, in this case it is confirmed the genotype-phenotype correlation described in most cases with large intragenic deletion of the c-terminal region of the AUTS2 gene. The early recognition of syndromic autism spectrum disorders by healthcare professionals allows, in addition to accurate genetic counseling, better multidisciplinary therapeutic management and consequently great benefits for patients and their families.

Keywords: AUTS2, AUTS2 syndrome, autism spectrum disorder, copy number variation, global developmental delay, syndromic autism