1. Truncating variants in PAPSS2 gene: A cause of early prenatal onset brachyolmia?
- Author
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Biancotto, Giulia, Rosti, Giulia, Madia, Francesca, Capra, Valeria, Scala, Marcello, Aleo, Elena, and Paladini, Dario
- Abstract
Brachyolmia is a rare form of skeletal dysplasia characterized by a wide genetic and clinical heterogeneity. This condition is usually diagnosed postnatally, and very few cases of prenatal diagnosis have been described so far. Here, we report a case of a pregnant woman at 20 weeks' gestation referred to our center because of fetal short long bones. On targeted ultrasound, mild bowing of the femurs and fibulae and mild micrognathia were also observed. Exome sequencing analysis showed the presence in compound heterozygosity of two pathogenic variants—both truncating variants—in the 3‐prime‐phosphoadenosine 5‐prime‐phosphosulfate synthase 2 (PAPSS2) gene, known to cause brachyolmia type 4 (OMIM #612847). Of note, all of the few cases reported prenatally have indeed truncating variants. Hence, we speculate this kind of variant is likely responsible for a complete loss of function of the protein leading to an earlier and more severe phenotype. Key points: What is already known on this topic? Brachyolmia shows a wide clinical heterogeneity and few cases have been described in fetuses. What does this study add? We report an early fetal diagnosis of brachyolmia, and speculate that the compound heterozygosity with two truncating mutations may be responsible for the prenatal onset of the bone shortening. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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