Novel PPP1R21 mutation in a family with autosomal recessive neurodevelopmental disorder: results of genomics and molecular analysis

Background Neurodevelopmental diseases are a group of disorders affecting the development of the nervous system and brain function. In particular, neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities is a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss-of-function variants. This study aimed to investigate the molecular etiology of this neurodevelopmental disorder in an Iranian patient from a consanguineous marriage family. Methods and results After clinical examination and DNA sampling, whole exome sequencing was performed for the patient. The findings were confirmed and segregated via Sanger sequencing and bioinformatics approach in the patient and parents, respectively. We identified the novel loss-of-function mutation of c.1317_1318delAG p.(Asp440Tyrfs*6) in PPP1R21 gene in our patient suffering from severe developmental delays, mental retardation, facial deformities, muscle weakness, difficulty breathing and feeding, and vision impairment. Through Sanger sequencing, the homozygous and heterozygous statuses of this variant were observed in the patient and the parents, respectively. As well, the bioinformatics approach demonstrated the disease-causing effect and clinical pathogenicity of this mutation. Conclusions Such findings improve our knowledge of patients with neurodevelopmental phenotypes. In addition, these results can be particularly helpful for prenatal and preimplantation diagnosis and genetic counseling of families with a high risk of infantile intellectual disabilities.