3q27.1 microdeletion causes prenatal and postnatal growth restriction and neurodevelopmental abnormalities

Subit Barua; Elaine M Pereira; Vaidehi Jobanputra; Kwame Anyane-Yeboa; Brynn Levy; Jun Liao

doi:10.1186/s13039-022-00587-0

3q27.1 microdeletion causes prenatal and postnatal growth restriction and neurodevelopmental abnormalities

Mol Cytogenet. 2022 Mar 3;15(1):7. doi: 10.1186/s13039-022-00587-0.

Authors

Subit Barua¹, Elaine M Pereira², Vaidehi Jobanputra³, Kwame Anyane-Yeboa², Brynn Levy³, Jun Liao⁴

Affiliations

¹ Department of Pathology, Anatomy, and Laboratory Medicine, West Virginia University Health Sciences Center, Morgantown, WV, USA.
² Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
³ Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
⁴ Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA. jl5098@cumc.columbia.edu.

Abstract

Background: Overlapping microdeletions of chromosome 3q26-3q28 have been reported in eight individuals. The common phenotype observed in these individuals include intrauterine growth restriction, short stature, microcephaly, feeding difficulties, facial dysmorphisms, limb abnormalities and developmental delay. The most striking clinical features shared among all reported cases is prenatal and postnatal growth restriction and neurodevelopmental abnormalities.

Case presentation: We 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.

Conclusions: This study provides further evidence supporting the existence of a novel 3q27.1 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.

Keywords: 3q27.1 microdeletion; AP2M1; CNV interpretation; DVL3; PARL.