Patient With Prolidase Deficiency due to an Homozygous PEPD Variant, Induced by Paternal Uniparental Isodisomy of...

Uniparental disomy (UPD) is a rare phenomenon in which both copies of a chromosome are inherited from a single parent. This can lead to genomic imprinting disorders and recessive disorders due to the presence of recessive pathogenic variants in both alleles. Additionally, depending on the mechanisms by which UPD occurs, mosaic aneuploidies may arise. Here we report the case of a patient with prenatal manifestations of intrauterine growth restriction and polyhydramnios, and postnatal manifestations of multiple congenital anomalies, developmental delay, and facial dysmorphisms. Prenatal exome sequencing targeting the fetal phenotype allowed the detection of uniparental isodisomy of chromosome 19. After birth, exome reanalysis revealed a homozygous pathogenic variant in the PEPD gene. This is the first case of prolidase deficiency due to UPD ever described. Prolidase deficiency is a low-prevalence disease with significant morbidity and mortality. Early diagnosis is essential to provide prognostic information, design an appropriate interdisciplinary follow-up program, and anticipate complications. This case highlights the importance of phenotypic assessment and postnatal clinical follow-up, as well as comprehensive genetic analyses to better understand complex phenotypes.