3p14 De Novo Interstitial Microdeletion in a Patient with Intellectual Disability and Autistic Features with Language Impairment: A Comparison with Similar Cases

Abstract

To date, few cases of 3p proximal interstitial deletions have been reported and the phenotype and genotype correlation is not well understood. Here, we report a new case of a 3p proximal interstitial deletion. The patient is an 11-year-old female with speech and social interaction difficulties, learning disability, and slight facial dysmorphism, but no other major malformations. An 8 Mb de novo interstitial deletion at 3p14.2-p14.1, from position 60.461.316 to 68.515.453, was revealed by means of array comparative genomic hybridization and confirmed using quantitative reverse-transcription polymerase chain reaction assays. This region includes six genes: FEZF2, CADPS, SYNPR, ATXN7, PRICKLE, and MAGI1, that are known to have a role in neurodevelopment. These genes are located on the proximal side of the deletion. We compare our case with previously well-defined patients reported in the literature and databases.

Figure 1

The facial photograph of the patient does not show any remarkable phenotypic features. Only slight facial dysmorphism could be observed: a long face with a prominent chin; broad forehead; and a broad, large mouth with widely spaced upper front teeth. Although not visible in this photograph, she has slightly protruding prominent ears.

Figure 2

The array comparative genomic hybridization (CGH) profile of chromosome 3 showing an interstitial deletion. (a) View of chromosome 3 and (b) the enlarged view of the rearrangement as generated by CytoGenomics v.2.7 (Agilent Technologies). The deletion breakpoint was between 60.461.316 and 68.515.453 (3p14.2-p14.1). The size of the deletion was ~8 Mb.

Figure 3

Schematic representation of the 3p14 deletions. The orange line represents the deletion in our patient. The deletions found by Okumura et al., Schwaibold et al., and Tao et al. are represented by lines in yellow, blue, and purple, respectively. The green and brown lines are deletions described previously in ISCA Consortium and DECIPHER databases, respectively. The thin red and black horizontal lines indicate the genes that are located in the 3p14 deleted region, the red ones being those that might be responsible for the phenotypic features given their known biological functions. The blue vertical dashed lines indicate the region in which the candidate genes are located and the overlapping deleted regions in 10 of the 11 cases.