Pre-Implantation Genetic Testing for Monogenic Disorders (PGT-M) in A Family with A Novel Mutation in DPAGT1 Gene

Tabatabaei, Zahra; Karbalaie, Khadijeh; Habibzadeh, Parham; Farazi Fard, Mohammad Ali; Faghihi, Mohammad Ali; Nasr Esfahani, Mohammad-Hossein

doi:10.22074/cellj.2021.7335

Pre-Implantation Genetic Testing for Monogenic Disorders (PGT-M) in A Family with A Novel Mutation in DPAGT1 Gene

Document Type : Case Report

Authors

¹ .Persian BayanGene Research and Training Center, Shiraz University of Medical Sciences, Shiraz, Iran

² .Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

³ .Persian BayanGene Research and Training Center, Shiraz University of Medical Sciences, Shiraz, Iran;.Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of

⁴ .Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran;4.Isfahan Fertility and Infertility Center, Isfahan, Iran

10.22074/cellj.2021.7335

Abstract

Congenital disorders of glycosylation (CDG) are a heterogeneous group of systemic disorders characterized by defects in glycosylation of lipids and proteins. One of the rare subtypes of CDG is CDG-Ij (MIM # 608093), which is caused by pathogenic mutations in DPAGT1, a gene encoding UDP-N-acetylglucosaminedolichyl-phosphate N-acetylglucosaminephosphotransferase enzyme. This enzyme catalyzes the first step of oligosaccharide synthesis in glycoprotein biosynthesis pathway. Preimplantation genetic testing for monogenic disorders (PGT-M) is a diagnostic technique that can reveal the genetic profile of embryos before implantation phase of in vitro fertilization (IVF). Currently, this approach is performed using next generation sequencing (NGS) technology. Herein, with the help of whole-exome and Sanger sequencing, we detected a novel missense mutation (NM_001382, c.1217 A>G) in DPAGT1 gene in two families with consanguineous marriage. Using different online bioinformatics tools including MutationTaster, I-Mutant v2.0, T- Coffee, and CADD v1.0, this mutation was predicted pathogen. Finally, after performing PGT-M followed by successful pregnancy, a normal child was born in one of these families. In conclusion, we identified a novel pathogenic mutation in DPAGT1 in a family with multiple members affected by CDG, which extends the range of pathogenic variants associated with CDG and therefore facilitates early detection of the disease.

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