Fetal Anomalies Associated with Novel Pathogenic Variants in TMEM94

Abstract

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 TMEM94 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 TMEM94 gene (c.606dupG and c.2729-2A>G) in two unrelated Saudi Arabian families. Conclusions: This study provides confirmation that TMEM94 variants may cause IDDCDF. For the first time we describe the pathogenicity of TMEM94 defects detected during the prenatal period.

Identification of Unusual Oxysterols Biosynthesised in Human Pregnancy by Charge-Tagging and Liquid Chromatography - Mass Spectrometry

“…At present we can only speculate, but the LXRactivating capacity of 22R-HC and 20R,22R-diHC and the expression of both LXRα and β during mammalian development makes it tempting to speculate that 20R-HC, 20R,22R-diHC and also 20S-HC by activating LXR, and in the case of 20S-HC by binding to Smo and Tmem97, are important for development of the embryo (Figure 9). In this regard, biallelic variants of Tmem97 were recently associated with fetal abnormalities (56). Little is known about the biological activities of trihydroxycholesterols and trihydroxycholestenoic acids and it is unknown whether 20R,22R,26-triHC, 3β,20R,22R-triHCA and 3β,20R,22R-triH-Δ 24 -CA are simply inactive intermediates on the road to bile acids or biologically active molecules themselves.…”

Evaluation of Calretinin and enumeration of mast cells in rectum tissue biopsies of Hirschsprung and non-Hirschsprung disease in neonate and infant

“…It has been shown that Consanguinity increases the likelihood that a husband and wife may have a gene that originated from a common ancestor. Numerous studies have shown that children of such a marriage are more likely to be homozygous for a dangerous gene and subsequently have autosomal recessive genetic diseases [75][76][77] . Other researchers, however, examined seven (25%) children with consanguineous parents who had HD (P = 1.000) and found no evidence of a connection between the two.…”