Two unrelated girls with intellectual disability associated with a truncating mutation in the PPM1D penultimate exon

Abstract PPM1D truncating mutations in the last and penultimate exons of the gene have been associated with intellectual disability (ID) syndrome. Only 15 affected patients to-date have been reported with mild-to-severe ID, autistic behavior, anxiety and dysmorphic features. Here, we describe the clinical characteristics and underlying genetics of two unrelated girls with moderate developmental delay and dysmorphic features associated with novel mutations in PPM1D exon 5. The dysmorphic features demonstrated by these two patients are consistent with previously reported patients, including broad forehead, thin upper lip, brachydactyly, and hypoplastic nails. We identified a de novo PPM1D mutation in exon 5 of each patient (c.1250_1251insACCA p.V419Tfs*16 and c.1256_1257insCAAG p.S421Qfs*14) by panel sequencing for 4,813 disease-related genes. Both patients also had frameshift mutations (at different positions) that resulted in the same estimated termination codon at 434. These additional reports add to the growing literature on PPM1D -associated ID syndrome and help delineate the clinical phenotype and genetic basis.