Abstract
Infantile hypotonia, with psychomotor retardation and characteristic facies 1 (IHPRF1), is a rare disorder characterized by global developmental delay and dysmorphic features. This syndrome is caused by genetic anomalies within the NALCN gene. The current report examines a 9-year-old female IHPRF1 patient. Our objective was to contribute to the delineation of the underlying factors influencing this rare condition. Whole exome sequencing (WES) was utilized to identify the disease-causing mutation in the affected individual. Subsequently, Sanger sequencing was performed for the patient, her parents, and two close relatives in order to confirm the detected mutation. Moreover, detailed clinical examinations including EEG, echocardiography, and biochemical/physical tests were carried out to elucidate the effects of the mutation. WES identified a homozygous nonsense mutation in the NALCN gene (c.2563C>T p.R855X). This mutation was confirmed by Sanger sequencing in the patient and her family members and segregated with the autosomal recessive inheritance pattern of IHPRF1. Moreover, genotype-phenotype correlation analysis confirmed the disease-causing nature of this mutation. The current report provides the first detailed description of a patient with this homozygous nonsense mutation (c.2563C>T p.R855X) and expands the clinical spectrum of IHPRF1 disease. Possible influences of sex and other factors on this disease are discussed and a review of the literature is also provided.