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. 2020 Aug 20;11(9):967.
doi: 10.3390/genes11090967.

Fetal Anomalies Associated with Novel Pathogenic Variants in TMEM94

Mohamed H Al-Hamed  1   2 , Nada Alsahan  3 , Maha Tulbah  3 , Wesam Kurdi  3 , Wafa'a Ali  2 , John A Sayer  4   5 , Faiqa Imtiaz  1   2
Affiliations

Fetal Anomalies Associated with Novel Pathogenic Variants in TMEM94

Mohamed H Al-Hamed et al. Genes (Basel). .

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.

Keywords: IDDCDF; TMEM94; consanguinity; pathogenic variant; prenatal exome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Antenatal ultrasound images of affected cases in family 1 (A,B) and family 2 (C,D). (A) Sagittal view of the fetal thorax and abdomen at 26 weeks of gestation, showing severe pleural effusion and ascites; (B) A transverse view of the fetal abdomen at 26 weeks of gestation showing ascites; (C) Coronal view of the fetal abdomen and pelvis at 29 weeks of gestation showing a well circumscribed hypoechoic area in the fetal abdomen which may represent an abdominal cyst with unknown origin; (D) Sagittal view of the fetal face at 29 weeks of gestation showing an abnormal profile with micrognathia.
Figure 2
Figure 2
Sequence chromatograms demonstrating novel variants detected and their locations in TMEM94 gene. (A) Schematic representation of exon structure of the TMEM94 gene, which is showing identified mutations. The location of c.606dupG and c.2729-2A>G mutations are shown by red arrows; (B,C) Sequencing chromatograms of the affected fetus, parent, and wild-type normal control of family 1 (B) and family 2 (C) in the TMEM94 gene (RefSeq NM_014738).
See this image and copyright information in PMC

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