Two novel deleterious variants of Angiotensin‐I‐converting Enzyme gene identified in a family with recurrent anhydramnios. Issue 6 (23rd April 2020)

• Record Type: Journal Article
• Authors: Wang, Jingwei; Bin, Qiao; Cheng, Biheng; Yan, Li; Xiong, Liang; Tan, Bi‐Hua; McGrath, Mary; Smink, Gayle M.; Song, Chunhua; Tong, Yongqing
• Is Part Of: Molecular genetics & genomic medicine. Volume 8:Issue 6(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-04-23
• Subjects: ACE -- anhydramnios -- Autosomal recessive renal tubular dysgenesis -- deleterious variants -- WES; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1239
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Anhydramnios results from the poor development of the placenta or problems with intrauterine development of the kidneys or urinary tract. Complete lack of amniotic fluid indicates a severe problem with the organs of the urinary system. The genes associated with anhydramnios show very diversity and are not yet well defined. Methods: Whole‐exome sequencing (WES) was used for an aborted male case around the 20th week of gestation diagnosed with anhydramnios. The resulted deleterious variants were verified by Sanger sequencing. Pathogenicity of deleterious variants was explored by in silico analysis. Results: A maternally inherited deleterious frameshift variant, c.1454_1455insC, p.(S486Ffs29) in exon 9 and two paternally inherited missense variants c.1037C > G, p.(Ser346Trp) in exon 7 and c.1465A > G, p.(Asn489Asp) in exon 9 of Angiotensin‐I‐Converting Enzyme ( ACE ) gene were found and confirmed by Sanger sequencing. c.1454_1455insC, p.(S486Ffs29) and c.1037C > G, p.(Ser346Trp) were identified as two novel compound heterozygous deleterious variants. The pathogenicity of these deleterious variants was determined by in silico analysis and both the deleterious variants disrupt the structure of the ACE protein. Conclusion: Two novel compound heterozygous variants were identified in the case with anhydramnios, which may be associated with pathogenicity of anhydramnios. Our data also revealed that the WES approach may provide helpful information for genetic counseling of the families with anhydramnios. Abstract : Two novel compound heterozygous deleterious variants in ACE were identified in the case with anhydramnios. Both the deleterious variants disrupt the structure of the ACE protein and in silico analysis indicates the pathogenicity of these deleterious variants. The identified novel genetic defects may be associated with the pathogenicity of anhydramnios. WES approach may provide helpful information for genetic counseling of the families with anhydramnios.