Microcephalic Osteodysplastic Primordial Dwarfism type II (
MOPDII) represents the most common form of primordial
dwarfism.
MOPD clinical features include severe prenatal and postnatal growth retardation, postnatal severe
microcephaly,
hypotonia, and an increased risk for
cerebrovascular disease and
insulin resistance. Autosomal recessive biallelic loss-of-function genomic variants in the centrosomal
pericentrin (PCNT) gene on chromosome 21q22 cause
MOPDII. Over the past decade, exome sequencing (ES) and massive
RNA sequencing have been effectively employed for both the discovery of novel disease genes and to expand the genotypes of well-known diseases. In this paper we report the results both the
RNA sequencing and ES of three patients affected by
MOPDII with the aim of exploring whether differentially expressed genes and previously uncharacterized gene variants, in addition to PCNT pathogenic variants, could be associated with the complex phenotype of this disease. We discovered a downregulation of key factors involved in growth, such as IGF1R, IGF2R, and RAF1, in all three investigated patients. Moreover, ES identified a shortlist of genes associated with deleterious, rare variants in
MOPDII patients. Our results suggest that Next Generation Sequencing (NGS) technologies can be successfully applied for the molecular characterization of the complex genotypic background of
MOPDII.