Microdeletions in the 9q22.3 chromosomal region can cause macrosomia with characteristic features, including prenatal-onset overgrowth, metopic craniosynostosis, hydrocephalus, developmental delay, and intellectual disability, in addition to manifestations of nevoid basal cell carcinoma syndrome (NBCCS). Haploinsufficiency of PTCH1 may be responsible for accelerated overgrowth, but the mechanism of macrosomia remains to be elucidated. We report a familial case with a 9q22.3 microdeletion, manifesting with prenatal-onset overgrowth in a mother and post-natal overgrowth in her daughter. Although both were clinically diagnosed with NBCCS, they had characteristic features of 9q22.3 microdeletion, especially the daughter. Microarray comparative genomic hybridization analysis revealed a 4.0 Mb deletion of chromosome 9q22.3 in both individuals. Among the 11 reported patients of overgrowth and/or macrosomia, a 550 Kb region encompassing PTCH1, C9orf3, FANCC, and 5 miRNAs is the most commonly deleted region. The let-7 family miRNAs, which are involved in diverse cellular processes including growth and tumor processes, were identified in the deleted regions in 10 of 11 patients. Characteristic features of 9q22.3 microdeletion might be associated with decreased expression of let-7.
Keywords: 9q22.3 microdeletion; Gorlin syndrome; Let-7; Overgrowth; PTCH1; miRNA.
Copyright © 2020. Published by Elsevier Masson SAS.