Genotype–phenotype correlation in eight new patients with a deletion encompassing 2q31.1

Abstract

Microdeletions of the 2q31.1 region are rare. We present the clinical and molecular findings of eight previously unreported patients with overlapping deletions in 2q31.1. The patients have a variable clinical phenotype and present with developmental delay (7/8), growth retardation (5/8), seizures (2/8) and a craniofacial dysmorphism consisting of microcephaly (4/8), short palpebral fissures (7/8), broad eyebrows with lateral flare (7/8), low-set ears with thickened helices and lobules (5/8), and micrognathia (6/8). Additional congenital anomalies were noted, including limb abnormalities (8/8), heart defects (3/8), genital anomalies (3/8), and craniosynostosis (1/8). Six of these microdeletions, ranging in size from 1.24 to 8.35 Mb, were identified by array CGH, one larger deletion (19.7 Mb) was detected by conventional karyotyping and further characterized by array CGH analysis. The smallest region of overlap in all eight patients spans at most 88 kb and includes only the WIPF1 gene. This gene codes for the WAS/WASL interacting protein family member 1. The patients described here do not present with clinical signs of the Wiskott-Aldrich syndrome and the deletion of this single gene does not allow explaining the phenotype in our patients. It is likely that the deletion of different but overlapping sets of genes from 2q31 is responsible for the clinical variability in these patients. To further dissect the complex phenotype associated with deletions in 2q31, additional patients with overlapping phenotypes should be examined with array CGH. This should help to link particular phenotypes to specific genes, and add to our understanding of the underlying developmental processes.