Novel De Novo Pathogenic Variant in the ODC1 Gene in a Girl with Developmental Delay, Alopecia, and Dysmorphic Features

The study reported a novel de novo pathogenic variant in the ODC1 gene in a 32-month-old Caucasian girl, marking the first human case with symptoms similar to those observed in a transgenic ODC1 mouse model. The identified heterozygous nonsense mutation in the ODC1 gene resulted in a premature termination of 14 amino acid residues at the protein's c-terminus. The patient exhibited phenotypic features such as developmental delay, alopecia, macrosomia, macrocephaly, spasticity, hypotonia, cutaneous vascular malformation, delayed visual maturation, and sensorineural hearing loss. Whole-exome sequencing and Sanger sequencing confirmed the mutation (c.1342 A>T), and elevated ODC protein and polyamine levels were found in the patient's red blood cells. The study suggested that the patient might benefit from treatment with α-difluoromethylornithine, an FDA-approved drug.