3q27.1 Microdeletion Causes a Clinically Recognizable Syndrome Characterized by Severe Prenatal and Postnatal Growth Restriction and Neurodevelopmental Abnormalities

BackgroundConstitutional deletions/rearrangements involving chromosome 3q are uncommon and overlapping microdeletions of chromosome 3q26-3q28 have only been reported in eight individuals. The common phenotype observed in these individuals include severe intrauterine growth restriction and postnatal growth impairment, feeding difficulties, characteristic facial features, feet abnormalities and developmental delay. The most striking clinical features shared among all reported cases is severe prenatal and postnatal growth restriction and neurodevelopmental abnormalities. Case presentationWe identified two additional individuals with overlapping deletions and shared clinical features by high-resolution SNP oligonucleotide microarray, and refined the smallest region of overlap (SRO) to a 1.2 Mb genomic location in chromosome 3q27.1 by reviewing and comparing all published cases. We evaluated the SRO using ACMG/ClinGen current recommendations for classifying copy number variants (CNVs), and discussed the contribution of the genes deleted in the SRO to the abnormal phenotype observed in these individuals. ConclusionsThis study provides further evidence supporting the existence of a novel 3q26q28 microdeletion syndrome and suggests that haploinsufficiency of potential candidate genes, DVL3, AP2M1, and PARL in the SRO in 3q27.1 is responsible for the phenotype. It also demonstrates the clinical utility of the newly released ACMG/Clingen standards for CNV interpretation.