Novel mutation in Patients with Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II)

Background A rare type of autosomal recessive skeletal disorder known as microcephalic osteodysplastic primordial dwarfism (MOPD) type II causes a wide range of clinical abnormalities, including skeletal dysplasia, microcephaly, abnormal skin pigmentation, Insulin resistance, typical facial features and severe tooth deformities. Owing to the diverse nature of MOPD disorders and common clinical characteristics of the Primordial dwarfism (PD) subtypes, mutation analysis is deemed essential for the precise diagnosis and validation of MOPD II. Here, Solo whole-exome sequencing (WES) and GAP-PCR were utilized to find relevant genetic variant(s) in three suspected MOPD patients. Method We assessed clinical characteristics of three Iranian patients with hallmarks of MOPD. There were two girls, ages 3 and 4, and a 2-year-old boy. All patients were the results of consanguineous marriages and referred to us from different provinces of Iran. WES was performed and the resulted variants were prioritized according to the standard filtration. In the next step, Sanger sequencing confirmation was conducted for validation of the derived variants by WES in the patients and their parents. Finally, we set up a GAP-PCR, based on conflicting results between WES and Sanger sequencing in one of the patients. Results Our results revealed a novel homozygous deletion (384bp) harboring exon 19 of PCNT in a 2-year-old boy. Additionally, we found a nonsense homozygous variant in PCNT gene (c.2812 C > T, p.Gln 938*) in two other patients. This pathogenic variant was clinically reported previously. Conclusion Reporting a novel deletion in PCNT gene leads to improvement in genetic testing services, including PND and pre-implantation genetic diagnosis (PGD) for MOPDII.