Fetal Anomalies Associated with Novel Pathogenic Variants in TMEM94.

Background: Intellectual developmental disorder with cardiac defects and dysmorphic facies (IDDCDF, MIM 618316) is a newly described disorder. It is characterized by global developmental delay, intellectual disability and speech delay, congenital cardiac malformations, and dysmorphic facial features. Biallelic pathogenic variants of are associated with IDDCDF.

Methods And Results: In a prenatal setting, where fetal abnormalities were detected using antenatal sonography, we used trio-exome sequencing (trio-ES) in conjunction with chromosomal microarray analysis (CMA) to identify two novel homozygous loss of function variants in the gene (c.606dupG and c.2729-2A>G) in two unrelated Saudi Arabian families.

Conclusions: This study provides confirmation that variants may cause IDDCDF. For the first time we describe the pathogenicity of defects detected during the prenatal period.