45. Examining potential candidate genes within deletions of 3p14.2 to 3p14.1 in two cases of autism and developmental delay

Copy number deletions at chromosomal region 3p14 are rare constitutional occurrences and the genes within this region are mainly unclassified. The small number of publications describing patients with 3p14 deletions list phenotypes of multiple congenital anomalies, movement disorders, feeding difficulties, developmental delay, and autism. Despite these recurring patient phenotypes, no potential candidate genes within this region have been identified.

Here we describe two unrelated cases with overlapping 3p14.2 to 3p14.1 single-copy deletions. The first case is a 5-year-old male with childhood apraxia of speech, global developmental delay, autism spectrum disorder, and hyperkinesis. This patient's deletion is 3.1 Mb in size and contains 15 known genes and 8 OMIM genes. The second case is a 2-year-old female with prematurity, global developmental delay, failure to thrive, feeding difficulties, feeding tube dependency, short stature, microcephaly, PDA closure, autism spectrum disorder, and abnormalities on brain MRI. This patient's deletion is 3.5 Mb in size and contains 24 known genes and 10 OMIM genes.

Taken together, 7 OMIM genes are deleted in both patients: PTPRG, FEZF2, CADPS, SNTN, THOC7, ATXN7, SCAANT1. We will explore how deletion of these potential candidate genes may impact the patients' shared phenotypes of autism and global developmental delay. Additionally, we will examine the three genes (PSMD6, PRICKLE2, ADAMTS9) that are deleted only in the second patient, who displays a more severe phenotype. This assessment may identify candidate genes for follow-up functional studies and will contribute to the literature by describing patients with rare copy number losses in this region.