EP05.52: New phenotype caused by novel compound heterozygous RARS2 or coincidence?

Recessive variants in RARS2, a nuclear gene encoding a mitochondrial protein, were initially reported in pontocerebellar hypoplasia type 6 (OMIM 611523). Highly heterogeneous clinical phenotypes and numerous missense variations of uncertain significance make diagnosis difficult. Pathogenesis of PCH6 remains unclear. Here we report a prenatal case of novel compound heterozygous with the new phenotype of brain lesions. A 31-year-old woman G1P0, was referred to our centre at 27 weeks of gestation due to suspected brain abnormalities. This pregnancy had amniocentesis with normal CMA at 16 weeks due to gastroschisis. Ultrasound and MRI in our centre revealed mild right ventriculomegaly 10mm, bilateral subependymal heterotopia, partial fused thalami, cleft of midbrain, suggested diencephalic mesencephalic junction dysplasia spectrum, asymmetric cerebellum with the smaller left hemispheres but normal TCD (at the 18th percentile) and pons, vermis hypoplasia and gastroschisis associated with severe fetal growth restriction. Trios exome sequencing was performed for further investigation and the result showed that fetus had novel compound heterozygous mutations NM_020320.5: c.1210A>G (p.Met404Val) and NM_020320.5: c.1187T>C (p.Val396Ala) in RARS2 gene inherited from each parents. We speculate that in RARS2 there is a highly heterogeneous clinical phenotypes. RARS2 testing should therefore also be performed in patients without pontocerebellar hypoplasia but otherwise brain lesions. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.